DOCSLIB.ORG

Reprogramming of H3k9me3-Dependent Heterochromatin During Mammalian Embryo Development

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Reprogramming of H3k9me3-Dependent Heterochromatin During Mammalian Embryo Development RESOURCE https://doi.org/10.1038/s41556-018-0093-4 Reprogramming of H3K9me3-dependent heterochromatin during mammalian embryo development Chenfei Wang 1,2, Xiaoyu Liu1,2, Yawei Gao 1,2*, Lei Yang1,2, Chong Li1, Wenqiang Liu1, Chuan Chen1, Xiaochen Kou1, Yanhong Zhao1, Jiayu Chen1, Yixuan Wang1, Rongrong Le1, Hong Wang1, Tao Duan1, Yong Zhang 1* and Shaorong Gao 1* H3K9me3-dependent heterochromatin is a major barrier of cell fate changes that must be reprogrammed after fertilization. However, the molecular details of these events are lacking in early embryos. Here, we map the genome-wide distribution of H3K9me3 modifications in mouse early embryos. We find that H3K9me3 exhibits distinct dynamic features in promoters and long terminal repeats (LTRs). Both parental genomes undergo large-scale H3K9me3 reestablishment after fertilization, and the imbalance in parental H3K9me3 signals lasts until blastocyst. The rebuilding of H3K9me3 on LTRs is involved in silencing their active transcription triggered by DNA demethylation. We identify that Chaf1a is essential for the establishment of H3K9me3 on LTRs and subsequent transcriptional repression. Finally, we find that lineage-specific H3K9me3 is established in post-implanta- tion embryos. In summary, our data demonstrate that H3K9me3-dependent heterochromatin undergoes dramatic reprogram- ming during early embryonic development and provide valuable resources for further exploration of the epigenetic mechanism in early embryos. ammals develop from fertilized eggs, which confer distinct To address the above questions, we performed comprehensive epigenetic modifications from both parental genomes. analyses of H3K9me3-dependent heterochromatin dynamics in MDuring fertilization, these epigenetic modifications pre-implantation mouse embryos as well as in differentiated embry- undergo extensive reprogramming for compatibility with embryonic onic tissues after implantation using a recently published ultra- totipotency1,2. Specifically, the constitutive heterochromatin marker low-input chromatin immunoprecipitation followed by sequencing histone 3 lysine 9 trimethylation (H3K9me3) is rapidly remodelled (ULI-NChIP–seq) method19,20. Based on this high-resolution map, to create a chromatin environment that is compatible with cellular we investigated the reprogramming of H3K9me3-dependent het- reprogramming and plasticity3. Meanwhile, H3K9me3-dependent erochromatin during mouse early embryonic development and also heterochromatin is also involved in embryonic gene regulation and explored the molecular mechanism of LTR silencing by H3K9me3- imprinted X inactivation during early embryonic development4–6. dependent heterochromatin in pre-implantation embryos. Depletion of the genes encoding H3K9me3-related chromatin fac- tors, such as Ehmt2 and Trim28, causes improper gene expression Results and embryonic lethality7,8. However, previous studies investigat- Genome-wide profiling of H3K9me3 in mouse gametes and ing the H3K9me3 dynamics in vivo based on immunofluorescence early embryos. We generated H3K9me3 profiles of mouse meta- staining have been limited by the imaging resolution and lack of an phase II (MII) oocytes, sperm and embryos from the zygote stage overarching regulatory framework9–11. Hence, genome-wide analy- (pronuclear stage 3 (PN3)) to embryonic day 8.5 (E8.5), mESCs ses of H3K9me3-dependent heterochromatin dynamics in pre- and mouse trophoblast stem cells (TSCs). Embryos at the blasto- implantation embryos are sorely needed. cyst stage were separated into the inner cell mass (ICM) and the The mouse genome is extensively demethylated during early trophectoderm, and post-implantation embryos were separated embryonic development12,13, and a large fraction of long termi- into epiblast and extraembryonic tissue (Fig. 1a,b). RNA sequenc- nal repeats (LTRs) become hypomethylated and are actively tran- ing (RNA-seq) and whole-genome bisulfite sequencing (WGBS), as scribed, which are crucial for normal development14,15. These LTRs well as ChIP–seq of the H3K4me3 and H3K27me3 levels (includ- must be properly regulated in later developmental stages to maintain ing some published data20) for each corresponding stage, were also genome stability16. Studies in mouse embryonic stem cells (mESCs) performed for comprehensive analysis (Supplementary Table 1). We have suggested that multiple H3K9me3 modifiers, such as Suv39h1/ found that the global H3K9me3 enrichment in ESCs generated from h2 and ERG-associated protein with SET domain (ESET) complexes, 500 cells was consistent with the ENCODE data from 10–20 mil- are responsible for retrovirus silencing by establishing H3K9me3 lion cells (Supplementary Fig. 1a). Moreover, the two replicates of modifications17,18. However, little is known about the involvement H3K9me3 for each embryonic stage had Pearson's correlation coef- of H3K9me3-dependent heterochromatin in LTR silencing during ficients > 0.9, indicating the high reproducibility of the H3K9me3 development in vivo. data (Supplementary Fig. 1b). 1Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China. 2These authors contributed equally: Chenfei Wang, Xiaoyu Liu, Yawei Gao and Lei Yang. *e-mail: [email protected]; [email protected]; [email protected] NATURE CELL BIOLOgy | www.nature.com/naturecellbiology © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. RESOURCE NATURE CELL BIOLOGY a MII E6.5 E7.5 Zygote2 cell 4 cell 8 cell Morula Blastocyst TE Exe Exe Sperm ICM Epi Epi b c Promoter region 100 kb mm9 Scale 10 kb mm9 Scale 3 H3K4me3 Chr7: Chr2: 174,130,000 11,700,000 11,800,000 2 H3K27me3 5 - MII 5 - 1 MII 0 _ H3K9me3 0 _ 5 - 0 5 - Sperm Sperm 0 _ −1 0 _ 5 - 5 - Zygote Zygote 0 _ 0 _ SINE region 5 - 5 - ) 2 cell 2 1.0 2 cell 0 _ 0 _ 5 - 5 - 4 cell 4 cell 0 _ 0.0 0 _ 5 - 5 - 8 cell 8 cell 0 _ 0 _ 5 - −1.0 5 - Morula Morula 0 _ 0 _ 5 - 5 - ICM ICM 0 _ 0 _ LINE region 5 - 5 - H3K9me3 TE TE H3K9me3 0 _ 0 _ 5 - 0.0 5 - E6.5 Epi E6.5 Epi 0 _ −1.0 0 _ 5 - 5 - E6.5 Exe E6.5 Exe 0 _ −2.0 0 _ 5 - 5 - E7.5 Epi Observed/expected ration (log E7.5 Epi 0 _ 0 _ 5 - 5 - E7.5 Exe LTR region E7.5 Exe 0 _ 0 _ 5 - 5 - E8.5 embryo 2.0 E8.5 embryo 0 _ 0 _ 5 - 1.0 5 - Encode.ESC Encode.ESC 0 _ 0 _ 5 - 0.0 5 - ESC ESC 0 _ −1.0 0 _ 5 - 5 - TSC TSC 0 _ 0 _ TE MII ICM Nespas Gnas Zscan4c Zscan4d 2 cell 4 cell 8 cell ESC TSC Zygote Morula LTR90B LTR E6.5 EpiE6.5 ExeE7.5 EpiE7.5 Exe E8.5 embryro de1.0 f 100 6 ) 5 80 0.5 ) 3 4 60 2 0.0 3 40 2 H3K9me3 domains (K) 1 −0.5 H3K9me3 domains (K) Number of LTRs marked by 20 Number of genes marked by 1 Fraction of total H3K9me3 regions (1 kb H3K9me3-marked regions compared to the genome (% 0 −1.0 0 0 TE TE TE TE MII ICM ICM MII ICM MII ICM 2 cel4l cel8l cell ESCTSC 2 cell 4 cell8 cell 2 cell4 cell8 cell ESC TSC 2 cell4 cell8 cell ESCTSC SpermZygote Morula Zygote Morula SperZygotm e Morula SperZygotm e Morula E6.5 E6.5ExeE7.5 EpiE7.5 Epi Exe E6.5E6.5 Epi ExeE7.5E7.5 Epi Exe E6.5E6.5 Epi ExeE7.5E7.5 Epi Exe E6.5E6.5 Epi E7.5ExeE7.5 Epi Exe E8.5 embryo E8.5 embryo E8.5 embryo E8.5 embryo Fig. 1 | Genome-wide profiling of H3K9me3 in mouse gametes and early embryos. a, Schematic showing the preparation of mouse embryos for genome- wide ChIP–seq analysis of H3K9me3. Samples of MII oocytes and sperm; zygotes, 2-cell-, 4-cell-, 8-cell- and morula-stage embryos; the ICM and the trophectoderm (TE) of E3.5 blastocysts; epiblast (Epi) and extraembryonic ectoderm (Exe) of E6.5 and E7.5 of post-implantation embryos are analysed. b, The UCSC genome browser view of H3K9me3 signals around Zscan4d (right panel) and Gnas (left panel) in mouse gametes, early embryos, mESCs (from either this study or from ENCODE) and mouse TSCs. Signals represent the log2-transformed H3K9me3/input ratio. Chr, chromosome. c, Bar plots show the enrichment of H3K9me3, H3K4me3 and H3K27me3 in promoter, SINE, LINE and LTR regions. d, Graph showing the percentage of genomic regions covered by H3K9me3 peaks. e, Graph showing the fraction of established and disappeared H3K9me3 domains during embryonic development. f, Graph showing the number of H3K9me3-marked LTR regions (left panel) and promoter regions (right panel) during embryonic development. In b–f, ChIP–seq for H3K9me3 was performed two times for each indicated stage, except for TSCs (three times) and E7.5 epiblast tissue (four times), and data shown represent the average values for each stage. In c, H3K4me3 and H3K27me3 ChIP–seq data for MII oocyte, sperm, 2-cell-, 4-cell-, 8-cell- and morula-stage embryos, E3.5 ICM, E3.5 trophectoderm and TSCs were from our previous publication (GSE73952)20 and others were derived from this study: H3K4me3 ChIP–seq was performed two times except for E7.5 epiblast and E7.5 extraembryonic tissues (three times), and H3K27me3 ChIP–seq was performed three times except for E7.5 epiblast and ESCs (two times). To identify H3K9me3-enriched domains during early embryonic chromatin using sequencing (ATAC-seq) signals at promoter regions development, we performed peak calling analysis using model-based and positively correlated with traditional repressive modifications analysis for ChIP-seq (MACS)21. We first examined the distribution (Supplementary Fig. 1d,e), reflecting the compatibility between of the H3K9me3 domains in early embryos and found that they are multiple epigenetic modifications in the regulation of embryonic distinct from H3K4me3 and H3K27me3 (Supplementary Fig.
Load more

Recommended publications
  • The Title of the Dissertation
    UNIVERSITY OF CALIFORNIA SAN DIEGO Novel network-based integrated analyses of multi-omics data reveal new insights into CD8+ T cell differentiation and mouse embryogenesis A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Bioinformatics and Systems Biology by Kai Zhang Committee in charge: Professor Wei Wang, Chair Professor Pavel Arkadjevich Pevzner, Co-Chair Professor Vineet Bafna Professor Cornelis Murre Professor Bing Ren 2018 Copyright Kai Zhang, 2018 All rights reserved. The dissertation of Kai Zhang is approved, and it is accept- able in quality and form for publication on microfilm and electronically: Co-Chair Chair University of California San Diego 2018 iii EPIGRAPH The only true wisdom is in knowing you know nothing. —Socrates iv TABLE OF CONTENTS Signature Page ....................................... iii Epigraph ........................................... iv Table of Contents ...................................... v List of Figures ........................................ viii List of Tables ........................................ ix Acknowledgements ..................................... x Vita ............................................. xi Abstract of the Dissertation ................................. xii Chapter 1 General introduction ............................ 1 1.1 The applications of graph theory in bioinformatics ......... 1 1.2 Leveraging graphs to conduct integrated analyses .......... 4 1.3 References .............................. 6 Chapter 2 Systematic
    [Show full text]
  • The Mutational Landscape of Myeloid Leukaemia in Down Syndrome
    cancers Review The Mutational Landscape of Myeloid Leukaemia in Down Syndrome Carini Picardi Morais de Castro 1, Maria Cadefau 1,2 and Sergi Cuartero 1,2,* 1 Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, 08916 Badalona, Spain; [email protected] (C.P.M.d.C); [email protected] (M.C.) 2 Germans Trias i Pujol Research Institute (IGTP), Campus Can Ruti, 08916 Badalona, Spain * Correspondence: [email protected] Simple Summary: Leukaemia occurs when specific mutations promote aberrant transcriptional and proliferation programs, which drive uncontrolled cell division and inhibit the cell’s capacity to differentiate. In this review, we summarize the most frequent genetic lesions found in myeloid leukaemia of Down syndrome, a rare paediatric leukaemia specific to individuals with trisomy 21. The evolution of this disease follows a well-defined sequence of events and represents a unique model to understand how the ordered acquisition of mutations drives malignancy. Abstract: Children with Down syndrome (DS) are particularly prone to haematopoietic disorders. Paediatric myeloid malignancies in DS occur at an unusually high frequency and generally follow a well-defined stepwise clinical evolution. First, the acquisition of mutations in the GATA1 transcription factor gives rise to a transient myeloproliferative disorder (TMD) in DS newborns. While this condition spontaneously resolves in most cases, some clones can acquire additional mutations, which trigger myeloid leukaemia of Down syndrome (ML-DS). These secondary mutations are predominantly found in chromatin and epigenetic regulators—such as cohesin, CTCF or EZH2—and Citation: de Castro, C.P.M.; Cadefau, in signalling mediators of the JAK/STAT and RAS pathways.
    [Show full text]
  • Steroid-Dependent Regulation of the Oviduct: a Cross-Species Transcriptomal Analysis
    University of Kentucky UKnowledge Theses and Dissertations--Animal and Food Sciences Animal and Food Sciences 2015 Steroid-dependent regulation of the oviduct: A cross-species transcriptomal analysis Katheryn L. Cerny University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Cerny, Katheryn L., "Steroid-dependent regulation of the oviduct: A cross-species transcriptomal analysis" (2015). Theses and Dissertations--Animal and Food Sciences. 49. https://uknowledge.uky.edu/animalsci_etds/49 This Doctoral Dissertation is brought to you for free and open access by the Animal and Food Sciences at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Animal and Food Sciences by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known.
    [Show full text]
  • Regulation of Oxidized Base Damage Repair by Chromatin Assembly Factor 1 Subunit a Chunying Yang1,*,†, Shiladitya Sengupta1,2,*,†, Pavana M
    Published online 27 October 2016 Nucleic Acids Research, 2017, Vol. 45, No. 2 739–748 doi: 10.1093/nar/gkw1024 Regulation of oxidized base damage repair by chromatin assembly factor 1 subunit A Chunying Yang1,*,†, Shiladitya Sengupta1,2,*,†, Pavana M. Hegde1,JoyMitra1, Shuai Jiang3, Brooke Holey3, Altaf H. Sarker3, Miaw-Sheue Tsai3, Muralidhar L. Hegde1,2,4 and Sankar Mitra1,2,* 1Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA, 2Weill Cornell Medical College, Cornell University, New York, NY 10065, USA, 3Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA and 4Houston Methodist Neurological Institute, Houston, TX 77030, USA Received March 23, 2016; Revised October 13, 2016; Editorial Decision October 17, 2016; Accepted October 19, 2016 ABSTRACT INTRODUCTION Reactive oxygen species (ROS), generated both en- ROS, continuously generated in mammalian cells both en- dogenously and in response to exogenous stress, in- dogenously and by environmental genotoxicants, induce duce point mutations by mis-replication of oxidized various genomic lesions, including oxidized bases, abasic bases and other lesions in the genome. Repair of (AP) sites and single-strand breaks (SSBs). If unrepaired or these lesions via base excision repair (BER) pathway mis-repaired, DNA lesions would cause mutations which may lead to cytotoxicity and cell death and also carcino- maintains genomic fidelity. Regulation of the BER genic transformation (1). The base excision repair (BER) pathway for mutagenic oxidized bases, initiated by pathway, responsible for repair of oxidized base lesions NEIL1 and other DNA glycosylases at the chromatin which contribute to drug/radiation sensitivity is highly con- level remains unexplored.
    [Show full text]
  • Supplementary Data
    SUPPLEMENTARY DATA A cyclin D1-dependent transcriptional program predicts clinical outcome in mantle cell lymphoma Santiago Demajo et al. 1 SUPPLEMENTARY DATA INDEX Supplementary Methods p. 3 Supplementary References p. 8 Supplementary Tables (S1 to S5) p. 9 Supplementary Figures (S1 to S15) p. 17 2 SUPPLEMENTARY METHODS Western blot, immunoprecipitation, and qRT-PCR Western blot (WB) analysis was performed as previously described (1), using cyclin D1 (Santa Cruz Biotechnology, sc-753, RRID:AB_2070433) and tubulin (Sigma-Aldrich, T5168, RRID:AB_477579) antibodies. Co-immunoprecipitation assays were performed as described before (2), using cyclin D1 antibody (Santa Cruz Biotechnology, sc-8396, RRID:AB_627344) or control IgG (Santa Cruz Biotechnology, sc-2025, RRID:AB_737182) followed by protein G- magnetic beads (Invitrogen) incubation and elution with Glycine 100mM pH=2.5. Co-IP experiments were performed within five weeks after cell thawing. Cyclin D1 (Santa Cruz Biotechnology, sc-753), E2F4 (Bethyl, A302-134A, RRID:AB_1720353), FOXM1 (Santa Cruz Biotechnology, sc-502, RRID:AB_631523), and CBP (Santa Cruz Biotechnology, sc-7300, RRID:AB_626817) antibodies were used for WB detection. In figure 1A and supplementary figure S2A, the same blot was probed with cyclin D1 and tubulin antibodies by cutting the membrane. In figure 2H, cyclin D1 and CBP blots correspond to the same membrane while E2F4 and FOXM1 blots correspond to an independent membrane. Image acquisition was performed with ImageQuant LAS 4000 mini (GE Healthcare). Image processing and quantification were performed with Multi Gauge software (Fujifilm). For qRT-PCR analysis, cDNA was generated from 1 µg RNA with qScript cDNA Synthesis kit (Quantabio). qRT–PCR reaction was performed using SYBR green (Roche).
    [Show full text]
  • Histone Modifications of H3k4me3, H3k9me3 and Lineage Gene Expressions in Chimeric Mouse Embryo
    Original Article Histone Modifications of H3K4me3, H3K9me3 and Lineage Gene Expressions in Chimeric Mouse Embryo Maryam Salimi, Ph.D.1, Abolfazl Shirazi, Ph.D.2, 3*, Mohsen Norouzian, Ph.D.1*, Mohammad Mehdi Mehrazar, M.Sc.2, Mohammad Mehdi Naderi, Ph.D.2, Mohammad Ali Shokrgozar, Ph.D.4, Mirdavood Omrani, Ph.D.5, Seyed Mahmoud Hashemi, Ph.D.6 1. Department of Biology and Anatomical Sciences, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2. Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran 3. Department of Gametes and Cloning, Research Institute of Animal Embryo Technology, Shahrekord University, Shahrekord, Iran 4. National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran 5. Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran 6. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran *Corresponding Addresses: P.O.Box: 19615/1177, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran P.O.Box: 1985717-443, Department of Biology and Anatomical Sciences, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Emails: [email protected], [email protected] Received: 4/October/2018, Accepted: 18/February/2019 Abstract Objective: Chimeric animal exhibits less viability and more fetal and placental abnormalities than normal animal. This study was aimed to determine the impact of mouse embryonic stem cells (mESCs) injection into the mouse embryos on H3K9me3 and H3K4me3 and cell lineage gene expressions in chimeric blastocysts. Materials and Methods: In our experiment, at the first step, incorporation of the GFP positive mESCs (GFP-mESCs) 129/Sv into the inner cell mass (ICM) of pre-compacted and compacted morula stage embryos was compared.
    [Show full text]
  • Histone Chaperone CHAF1A Inhibits Differentiation and Promotes Aggressive Neuroblastoma
    Published OnlineFirst December 12, 2013; DOI: 10.1158/0008-5472.CAN-13-1315 Cancer Molecular and Cellular Pathobiology Research Histone Chaperone CHAF1A Inhibits Differentiation and Promotes Aggressive Neuroblastoma Eveline Barbieri1, Katleen De Preter3, Mario Capasso4, Zaowen Chen1, Danielle M. Hsu2, Gian Paolo Tonini5, Steve Lefever3, John Hicks1, Rogier Versteeg7, Andrea Pession6, Frank Speleman3, Eugene S. Kim2, and Jason M. Shohet1 Abstract Neuroblastoma arises from the embryonal neural crest secondary to a block in differentiation. Long-term patient survival correlates inversely with the extent of differentiation, and treatment with retinoic acid or other prodifferentiation agents improves survival modestly. In this study, we show the histone chaperone and epigenetic regulator CHAF1A functions in maintaining the highly dedifferentiated state of this aggressive malignancy. CHAF1A is a subunit of the chromatin modifier chromatin assembly factor 1 and it regulates H3K9 trimethylation of key target genes regulating proliferation, survival, and differentiation. Elevated CHAF1A expression strongly correlated with poor prognosis. Conversely, CHAF1A loss-of-function was sufficient to drive neuronal differentiation in vitro and in vivo. Transcriptome analysis of cells lacking CHAF1A revealed repression of oncogenic signaling pathways and a normalization of glycolytic metabolism. Our findings demonstrate that CHAF1A restricts neural crest differentiation and contributes to the pathogenesis of high-risk neuroblastoma. Cancer Res; 74(3); 1–10.
    [Show full text]
  • Simultaneous Epigenetic Perturbation and Genome Imaging Reveal Distinct Roles of H3k9me3 in Chromatin Architecture and Transcription
    University of Massachusetts Medical School eScholarship@UMMS Open Access Publications by UMMS Authors 2020-12-08 Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription Ying Feng East China University of Science and Technology Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/oapubs Part of the Amino Acids, Peptides, and Proteins Commons, Genetics and Genomics Commons, and the Structural Biology Commons Repository Citation Feng Y, Wang Y, Wang X, He X, Yang C, Naseri A, Pederson T, Zheng J, Zhang S, Xiao X, Xie W, Ma H. (2020). Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription. Open Access Publications by UMMS Authors. https://doi.org/ 10.1186/s13059-020-02201-1. Retrieved from https://escholarship.umassmed.edu/oapubs/4502 Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 License. This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Open Access Publications by UMMS Authors by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. Feng et al. Genome Biology (2020) 21:296 https://doi.org/10.1186/s13059-020-02201-1 RESEARCH Open Access Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription Ying Feng1†, Yao Wang2,3†, Xiangnan Wang4, Xiaohui He4, Chen Yang5, Ardalan Naseri6, Thoru Pederson7, Jing Zheng5, Shaojie Zhang6, Xiao Xiao8, Wei Xie2,3* and Hanhui Ma4* * Correspondence: xiewei121@ tsinghua.edu.cn; mahh@ Abstract shanghaitech.edu.cn †Ying Feng and Yao Wang Introduction: Despite the long-observed correlation between H3K9me3, chromatin contributed equally to this work.
    [Show full text]
  • A Dissertation Entitled the Androgen Receptor
    A Dissertation entitled The Androgen Receptor as a Transcriptional Co-activator: Implications in the Growth and Progression of Prostate Cancer By Mesfin Gonit Submitted to the Graduate Faculty as partial fulfillment of the requirements for the PhD Degree in Biomedical science Dr. Manohar Ratnam, Committee Chair Dr. Lirim Shemshedini, Committee Member Dr. Robert Trumbly, Committee Member Dr. Edwin Sanchez, Committee Member Dr. Beata Lecka -Czernik, Committee Member Dr. Patricia R. Komuniecki, Dean College of Graduate Studies The University of Toledo August 2011 Copyright 2011, Mesfin Gonit This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of The Androgen Receptor as a Transcriptional Co-activator: Implications in the Growth and Progression of Prostate Cancer By Mesfin Gonit As partial fulfillment of the requirements for the PhD Degree in Biomedical science The University of Toledo August 2011 Prostate cancer depends on the androgen receptor (AR) for growth and survival even in the absence of androgen. In the classical models of gene activation by AR, ligand activated AR signals through binding to the androgen response elements (AREs) in the target gene promoter/enhancer. In the present study the role of AREs in the androgen- independent transcriptional signaling was investigated using LP50 cells, derived from parental LNCaP cells through extended passage in vitro. LP50 cells reflected the signature gene overexpression profile of advanced clinical prostate tumors. The growth of LP50 cells was profoundly dependent on nuclear localized AR but was independent of androgen. Nevertheless, in these cells AR was unable to bind to AREs in the absence of androgen.
    [Show full text]
  • Deciphering the Histone Code to Build the Genome Structure
    bioRxiv preprint doi: https://doi.org/10.1101/217190; this version posted November 20, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Deciphering the histone code to build the genome structure Kirti Prakasha,b,c,* and David Fournierd,* aPhysico-Chimie Curie, Institut Curie, CNRS UMR 168, 75005 Paris, France; bOxford Nanoimaging Ltd, OX1 1JD, Oxford, UK; cMicron Advanced Bioimaging Unit, Department of Biochemistry, University of Oxford, Oxford, UK; dFaculty of Biology and Center for Computational Sciences, Johannes Gutenberg University Mainz, 55128 Mainz, Germany; *Correspondence: [email protected], [email protected] Histones are punctuated with small chemical modifications that alter their interaction with DNA. One attractive hypothesis stipulates that certain combinations of these histone modifications may function, alone or together, as a part of a predictive histone code to provide ground rules for chromatin folding. We consider four features that relate histone modifications to chromatin folding: charge neutrali- sation, molecular specificity, robustness and evolvability. Next, we present evidence for the association among different histone modi- fications at various levels of chromatin organisation and show how these relationships relate to function such as transcription, replica- tion and cell division. Finally, we propose a model where the histone code can set critical checkpoints for chromatin to fold reversibly be- tween different orders of the organisation in response to a biological stimulus. DNA | nucleosomes | histone modifications | chromatin domains | chro- mosomes | histone code | chromatin folding | genome structure Introduction The genetic information within chromosomes of eukaryotes is packaged into chromatin, a long and folded polymer of double-stranded DNA, histones and other structural and non- structural proteins.
    [Show full text]
  • Dynamics of Transcription-Dependent H3k36me3 Marking by the SETD2:IWS1:SPT6 Ternary Complex
    bioRxiv preprint doi: https://doi.org/10.1101/636084; this version posted May 14, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Dynamics of transcription-dependent H3K36me3 marking by the SETD2:IWS1:SPT6 ternary complex Katerina Cermakova1, Eric A. Smith1, Vaclav Veverka2, H. Courtney Hodges1,3,4,* 1 Department of Molecular & Cellular Biology, Center for Precision Environmental Health, and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA 2 Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic 3 Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA 4 Department of Bioengineering, Rice University, Houston, TX, 77005, USA * Lead contact; Correspondence to: [email protected] Abstract The genome-wide distribution of H3K36me3 is maintained SETD2 contributes to gene expression by marking gene through various mechanisms. In human cells, H3K36 is bodies with H3K36me3, which is thought to assist in the mono- and di-methylated by eight distinct histone concentration of transcription machinery at the small portion methyltransferases; however, the predominant writer of the of the coding genome. Despite extensive genome-wide data trimethyl mark on H3K36 is SETD21,11,12. Interestingly, revealing the precise localization of H3K36me3 over gene SETD2 is a major tumor suppressor in clear cell renal cell bodies, the physical basis for the accumulation, carcinoma13, breast cancer14, bladder cancer15, and acute maintenance, and sharp borders of H3K36me3 over these lymphoblastic leukemias16–18. In these settings, mutations sites remains rudimentary.
    [Show full text]
  • Differential Expression Profile Analysis of DNA Damage Repair Genes in CD133+/CD133‑ Colorectal Cancer Cells
    ONCOLOGY LETTERS 14: 2359-2368, 2017 Differential expression profile analysis of DNA damage repair genes in CD133+/CD133‑ colorectal cancer cells YUHONG LU1*, XIN ZHOU2*, QINGLIANG ZENG2, DAISHUN LIU3 and CHANGWU YUE3 1College of Basic Medicine, Zunyi Medical University, Zunyi; 2Deparment of Gastroenterological Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi;3 Zunyi Key Laboratory of Genetic Diagnosis and Targeted Drug Therapy, The First People's Hospital of Zunyi, Zunyi, Guizhou 563003, P.R. China Received July 20, 2015; Accepted January 6, 2017 DOI: 10.3892/ol.2017.6415 Abstract. The present study examined differential expression cells. By contrast, 6 genes were downregulated and none levels of DNA damage repair genes in COLO 205 colorectal were upregulated in the CD133+ cells compared with the cancer cells, with the aim of identifying novel biomarkers for COLO 205 cells. These findings suggest that CD133+ cells the molecular diagnosis and treatment of colorectal cancer. may possess the same DNA repair capacity as COLO 205 COLO 205-derived cell spheres were cultured in serum-free cells. Heterogeneity in the expression profile of DNA damage medium supplemented with cell factors, and CD133+/CD133- repair genes was observed in COLO 205 cells, and COLO cells were subsequently sorted using an indirect CD133 205-derived CD133- cells and CD133+ cells may therefore microbead kit. In vitro differentiation and tumorigenicity assays provide a reference for molecular diagnosis, therapeutic target in BABA/c nude mice were performed to determine whether selection and determination of the treatment and prognosis for the CD133+ cells also possessed stem cell characteristics, in colorectal cancer.
    [Show full text]