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Interaction and Functional Cooperation of the Cancer-Amplified Transcriptional Coactivator Activating Signal Cointegrator-2 and E2F-1 in Cell Proliferation
948 Vol. 1, 948–958, November 2003 Molecular Cancer Research Interaction and Functional Cooperation of the Cancer-Amplified Transcriptional Coactivator Activating Signal Cointegrator-2 and E2F-1 in Cell Proliferation Hee Jeong Kong,1 Hyun Jung Yu,2 SunHwa Hong,2 Min Jung Park,2 Young Hyun Choi,3 Won Gun An,4 Jae Woon Lee,5 and JaeHun Cheong2 1Laboratory of Molecular Growth Regulation, National Institute of Health, Bethesda, MD; 2Department of Molecular Biology, Pusan National University, Busan, Republic of Korea; 3Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, Republic of Korea; 4Department of Biology, Kyungpook National University, DaeGu, Republic of Korea; and 5Department of Medicine/Endocrinology, Baylor College of Medicine Houston, TX. Abstract structure and recruitment of a transcription initiation complex Activating signal cointegrator-2 (ASC-2), a novel coac- containing RNA polymerase II to the promoter (1). Recent tivator, is amplified in several cancer cells and known to studies have shown that DNA-bound transcriptional activator interact with mitogenic transcription factors, including proteins accomplish these two tasks with the assistance of a serum response factor, activating protein-1, and nuclear class of proteins called transcriptional coactivators (2, 3). They factor-KB, suggesting the physiological role of ASC-2 in may be thought of as adaptors or components in a signaling the promotion of cell proliferation. Here, we show that pathway that transmits transcriptional activation signals from the expression pattern of ASC-2 was correlated with that DNA-bound activator proteins to the chromatin and transcrip- of E2F-1 for protein increases at G1 and S phase. -
Chromatin Remodeling in Mice
University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Supervised Undergraduate Student Research Chancellor’s Honors Program Projects and Creative Work Spring 5-2005 Chromatin Remodeling in Mice Stephen James Dolgner University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_chanhonoproj Recommended Citation Dolgner, Stephen James, "Chromatin Remodeling in Mice" (2005). Chancellor’s Honors Program Projects. https://trace.tennessee.edu/utk_chanhonoproj/843 This is brought to you for free and open access by the Supervised Undergraduate Student Research and Creative Work at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Chancellor’s Honors Program Projects by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. Chromatin Remodeling in Mice Stephen Dolgner Advisor: Dr. Sundaresan Venkatachalam May 2005 ABSTRACT Controlling gene regulation is an important aspect in the life of cells that provides them the ability to carry out their functional roles within an organism. Unregulated or misregulated gene expression can lead to cell immortalization or death. Chromatin remodeling functions as a regulator for many important DNA functions including transcription, the first step of gene expression in cells. The Chromodomain-Helicase DNA binding domain gene family (CHD) is evolutionarily conserved and has distinct structural motifs that indicate a role in chromatin remodeling and DNA repair. The CHD proteins have both helicase activity, allowing the winding and unwinding of DNA, and an effect on histone acetylation through their role of the Nucleosome Remodeling and Histone Deacetylation (NuRD) complex. The NuRD complex participates in the deacetylation of chromatin histones, in addition to orchestrating ATP-dependent remodeling of the the chromatin structure. -
The Yin and Yang of Enhancer–Promoter Interactions
RESEARCH HIGHLIGHTS Nature Reviews Molecular Cell Biology | Published online 20 Dec 2017; doi:10.1038/nrm.2017.136 GENE EXPRESSION in the promoters of two genes resulted in reduced YY1 binding, reduced contact frequency between the pro- The yin and yang of enhancer– moters and their cognate enhancers and, in one of the genes, reduced expression. The lack of reduced promoter interactions expression of one of the genes was probably due to YY1 binding at Transcription factors can facilitate the could bind to these elements and facil- other, less optimal motifs; indeed, physical interaction between enhanc- itate their interaction. They identified YY1 depletion resulted in decreased ers and promoters and looping of deletion of another zinc finger protein, YY1, expression of both genes. the intervening DNA between them. YY1 binding which, like CTCF, is essential for cell Next, using an inducible protein Such loops are formed within larger, viability and is ubiquitously expressed. degradation system, the genome-wide insulated chromosomal loops (also motifs… Importantly, co- immunoprecipitation effects of YY1 depletion were meas- known as topologically associating reduced of differentially tagged YY1 proteins ured. The expression of thousands domains (TADs)), which are formed contact confirmed that YY1 can form of genes was changed (increased or by dimerization of the zinc finger frequency homodimers. decreased), and in general the genes protein CTCF bound to chromatin. In various mouse and human cell with the greatest changes following Weintraub et al. now show that, anal- between the types, YY1 occupied enhancers and YY1 depletion were those with ogously to CTCF, the protein yin and promoters and promoters genome-wide. -
A Curated Benchmark of Enhancer-Gene Interactions for Evaluating Enhancer-Target Gene Prediction Methods
University of Massachusetts Medical School eScholarship@UMMS Open Access Articles Open Access Publications by UMMS Authors 2020-01-22 A curated benchmark of enhancer-gene interactions for evaluating enhancer-target gene prediction methods Jill E. Moore University of Massachusetts Medical School 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 Bioinformatics Commons, Computational Biology Commons, Genetic Phenomena Commons, and the Genomics Commons Repository Citation Moore JE, Pratt HE, Purcaro MJ, Weng Z. (2020). A curated benchmark of enhancer-gene interactions for evaluating enhancer-target gene prediction methods. Open Access Articles. https://doi.org/10.1186/ s13059-019-1924-8. Retrieved from https://escholarship.umassmed.edu/oapubs/4118 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 Articles by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. Moore et al. Genome Biology (2020) 21:17 https://doi.org/10.1186/s13059-019-1924-8 RESEARCH Open Access A curated benchmark of enhancer-gene interactions for evaluating enhancer-target gene prediction methods Jill E. Moore, Henry E. Pratt, Michael J. Purcaro and Zhiping Weng* Abstract Background: Many genome-wide collections of candidate cis-regulatory elements (cCREs) have been defined using genomic and epigenomic data, but it remains a major challenge to connect these elements to their target genes. Results: To facilitate the development of computational methods for predicting target genes, we develop a Benchmark of candidate Enhancer-Gene Interactions (BENGI) by integrating the recently developed Registry of cCREs with experimentally derived genomic interactions. -
An HMG I/Y-Containing Repressor Complex and Supercolled DNA Topology Are Critical for Long-Range Enhancer-Dependent Transcription in Vitro
Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press An HMG I/Y-containing repressor complex and supercolled DNA topology are critical for long-range enhancer-dependent transcription in vitro Rajesh Bagga and Beverly M. Emerson 1 Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037 USA The 3' enhancer of the T cell receptor s.chain (TCR~) gene directs the tissue- and stage-specific expression and V(D)Jrecombination of this gene locus. Using an in vitro system that reproduces TCRoL enhancer activity efficiently, we show that long-range promoter-enhancer regulation requires a T cell-specific repressor complex and is sensitive to DNA topology. In this system, the enhancer functions to derepress the promoter on supercoiled, but not relaxed, templates. We find that the TCRoL promoter is inactivated by a repressor complex that contains the architectural protein HMG I/Y. In the absence of this repressor complex, expression of the TCR~ gene is completely independent of the 3' enhancer and DNA topology. The interaction of the T cell-restricted protein LEF-1 with the TCR~ enhancer is required for promoter derepression. In this system, the TCR~ enhancer increases the number of active promoters rather than the rate of transcription. Thus, long-range enhancers function in a distinct manner from promoters and provide the regulatory link between repressors, DNA topology, and gene activity. [Key Words: TCR genes; transcription; enhancers; HMG I/Y; derepression; DNA topology] Received December 27, 1996; revised version accepted January 14, 1997. The widespread importance of long-range promoter- Giaever 1988; Rippe et al. -
Promoter Methylation Status for Cell-Type Deconvolution
bioRxiv preprint doi: https://doi.org/10.1101/2021.01.28.428654; this version posted January 29, 2021. 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. Long Reads Capture Simultaneous Enhancer- Promoter Methylation Status for Cell-type Deconvolution Sapir Margalit1,2, Yotam Abramson1,2, Hila Sharim1,2, Zohar Manber2,3, Surajit Bhattacharya4, Yi-Wen Chen4,5, Eric Vilain4,5, Hayk Barseghyan4,5, Ran Elkon2,3, Roded Sharan2,6* and Yuval Ebenstein1,2* 1Department of physical chemistry, Tel Aviv University, Tel Aviv 6997801, Israel., 2Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv, Israel., 3Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel., 4Center for Genetic Medicine Research, Children’s National Hospital, 111 Michigan Avenue NW, Washington DC 20010, USA., 5Department of Genomics and Precision Medicine, George Washington University 1918 F Street, NW Washington, DC 20052, USA., 6School of Computer Science, Tel-Aviv University, Tel-Aviv 6997801, Israel.*Corresponding Author Abstract Motivation: While promoter methylation is associated with reinforcing fundamental tissue identities, the methylation status of distant enhancers was shown by genome-wide association studies to be a powerful determinant of cell-state and cancer. With recent availability of long-reads that report on the methylation status of enhancer-promoter pairs on the same molecule, we hypothesized that probing these pairs on the single-molecule level may serve the basis for detection of rare cancerous transformations in a given cell population. We explore various analysis approaches for deconvolving cell-type mixtures based on their genome-wide enhancer-promoter methylation profiles. -
Original Article EP300 Regulates the Expression of Human Survivin Gene in Esophageal Squamous Cell Carcinoma
Int J Clin Exp Med 2016;9(6):10452-10460 www.ijcem.com /ISSN:1940-5901/IJCEM0023383 Original Article EP300 regulates the expression of human survivin gene in esophageal squamous cell carcinoma Xiaoya Yang, Zhu Li, Yintu Ma, Xuhua Yang, Jun Gao, Surui Liu, Gengyin Wang Department of Blood Transfusion, The Bethune International Peace Hospital of China PLA, Shijiazhuang 050082, Hebei, P. R. China Received January 6, 2016; Accepted March 21, 2016; Epub June 15, 2016; Published June 30, 2016 Abstract: Survivin is selectively up-regulated in various cancers including esophageal squamous cell carcinoma (ESCC). The underlying mechanism of survivin overexpression in cancers is needed to be further studied. In this study, we investigated the effect of EP300, a well known transcriptional coactivator, on survivin gene expression in human esophageal squamous cancer cell lines. We found that overexpression of EP300 was associated with strong repression of survivin expression at the mRNA and protein levels. Knockdown of EP300 increased the survivin ex- pression as indicated by western blotting and RT-PCR analysis. Furthermore, our results indicated that transcription- al repression mediated by EP300 regulates survivin expression levels via regulating the survivin promoter activity. Chromatin immunoprecipitation (ChIP) analysis revealed that EP300 was associated with survivin gene promoter. When EP300 was added to esophageal squamous cancer cells, increased EP300 association was observed at the survivin promoter. But the acetylation level of histone H3 at survivin promoter didn’t change after RNAi-depletion of endogenous EP300 or after overexpression of EP300. These findings establish a negative regulatory role for EP300 in survivin expression. Keywords: Survivin, EP300, transcription regulation, ESCC Introduction transcription factors and the basal transcrip- tion machinery, or by providing a scaffold for Survivin belongs to the inhibitor of apoptosis integrating a variety of different proteins [6]. -
Crystal Structure of the Bacteriophage T4 Late-Transcription Coactivator Gp33 with the Β-Subunit Flap Domain of Escherichia Coli RNA Polymerase
Crystal structure of the bacteriophage T4 late-transcription coactivator gp33 with the β-subunit flap domain of Escherichia coli RNA polymerase The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Twist, K.-A. F., E. A. Campbell, P. Deighan, S. Nechaev, V. Jain, E. P. Geiduschek, A. Hochschild, and S. A. Darst. 2011. “Crystal Structure of the Bacteriophage T4 Late-Transcription Coactivator gp33 with the -Subunit Flap Domain of Escherichia Coli RNA Polymerase.” Proceedings of the National Academy of Sciences 108 (50): 19961– 66. https://doi.org/10.1073/pnas.1113328108. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483152 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Crystal structure of the bacteriophage T4 late- transcription coactivator gp33 with the β-subunit flap domain of Escherichia coli RNA polymerase Kelly-Anne F. Twista,1, Elizabeth A. Campbella, Padraig Deighanb, Sergei Nechaevc,2, Vikas Jainc,3, E. Peter Geiduschekc, Ann Hochschildb, and Seth A. Darsta,4 aLaboratory of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10065; bDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; and cDivision of Biological Sciences, Section of Molecular Biology, University -
The Gene Repressor Complex Nurd Interacts with the Histone Variant H3.3
Downloaded from genome.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press The gene repressor complex NuRD interacts with the histone variant H3.3 at promoters of active genes Daniel C. Kraushaar1,3,4, Zuozhou Chen2,4, Qingsong Tang1, Kairong Cui1, Junfang Zhang2,*, Keji Zhao1,* 1 Systems Biology Center, National Heart, Lung, and Blood Institute, NIH, MD 2 Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Shanghai Ocean University), Ministry of Education; International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China. 3 Current address: Genomic and RNA Profiling Core, Baylor College of Medicine, TX 4These authors contributed equally to this work *Correspondence: Junfang Zhang ([email protected]); Keji Zhao ([email protected]) Key words: histone variant H3.3; chromatin modification; epigenetics; ChIP-seq; protein interaction; NuRD; histone modification 1 Downloaded from genome.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press Abstract The histone variant H3.3 is deposited across active genes, regulatory regions and telomeres. It remains unclear how H3.3 interacts with chromatin modifying enzymes and thereby modulates gene activity. In this study, we performed a co- immunoprecipitation-mass spectrometry analysis of proteins associated with H3.3-containing nucleosomes and identified the Nucleosome Remodeling and Deacetylase complex (NuRD) as a major H3.3-interactor. We show that the H3.3- NuRD interaction is dependent on the H3.3 lysine 4 residue and that NuRD binding occurs when lysine 4 is in its unmodified state. -
Molecular Basis of the Function of Transcriptional Enhancers
cells Review Molecular Basis of the Function of Transcriptional Enhancers 1,2, 1, 1,3, Airat N. Ibragimov y, Oleg V. Bylino y and Yulii V. Shidlovskii * 1 Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia; [email protected] (A.N.I.); [email protected] (O.V.B.) 2 Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov St., 119334 Moscow, Russia 3 I.M. Sechenov First Moscow State Medical University, 8, bldg. 2 Trubetskaya St., 119048 Moscow, Russia * Correspondence: [email protected]; Tel.: +7-4991354096 These authors contributed equally to this study. y Received: 30 May 2020; Accepted: 3 July 2020; Published: 5 July 2020 Abstract: Transcriptional enhancers are major genomic elements that control gene activity in eukaryotes. Recent studies provided deeper insight into the temporal and spatial organization of transcription in the nucleus, the role of non-coding RNAs in the process, and the epigenetic control of gene expression. Thus, multiple molecular details of enhancer functioning were revealed. Here, we describe the recent data and models of molecular organization of enhancer-driven transcription. Keywords: enhancer; promoter; chromatin; transcriptional bursting; transcription factories; enhancer RNA; epigenetic marks 1. Introduction Gene transcription is precisely organized in time and space. The process requires the participation of hundreds of molecules, which form an extensive interaction network. Substantial progress was achieved recently in our understanding of the molecular processes that take place in the cell nucleus (e.g., see [1–9]). -
Structure, Function, and Evolution of a Signal-Regulated Enhancer
Structure, Function, and Evolution of a Signal-Regulated Enhancer by Christina Ione Swanson A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Cell and Developmental Biology) in the University of Michigan 2010 Doctoral Committee: Assistant Professor Scott E. Barolo, Chair Professor J. Douglas Engel Associate Professor Kenneth M. Cadigan Associate Professor Billy Tsai Assistant Professor Patricia J. Wittkopp To my family, for your truly unconditional love and support. And to Mike - the best thing that happened to me in grad school. ii TABLE OF CONTENTS DEDICATION .................................................................................................................. ii LIST OF FIGURES ............................................................................................................ v CHAPTER I: INTRODUCTION ....................................................................................... 1 What do enhancers look like? ................................................................................ 2 Mechanisms of enhancer function ......................................................................... 3 Enhancer structure and organization ...................................................................... 6 Unanswered questions in the field ....................................................................... 10 The D-Pax2 sparkling enhancer .......................................................................... 12 CHAPTER II: STRUCTURAL RULES -
Enhancer Rnas Are an Important Regulatory Layer of the Epigenome
REVIEW ARTICLE https://doi.org/10.1038/s41594-020-0446-0 Enhancer RNAs are an important regulatory layer of the epigenome Vittorio Sartorelli 1 and Shannon M. Lauberth 2 ✉ Noncoding RNAs (ncRNAs) direct a remarkable number of diverse functions in development and disease through their regula- tion of transcription, RNA processing and translation. Leading the charge in the RNA revolution is a class of ncRNAs that are synthesized at active enhancers, called enhancer RNAs (eRNAs). Here, we review recent insights into the biogenesis of eRNAs and the mechanisms underlying their multifaceted functions and consider how these findings could inform future investigations into enhancer transcription and eRNA function. he explosion of high-throughput sequencing data has Many different models for how enhancers function in gene con- revealed the complexity and diversity of the transcriptome. trol have been proposed since their initial discovery nearly four TThese data have also unexpectedly revealed that only 1–2% decades ago19–21. Specifically, there is considerable evidence demon- of the transcriptome provides instructions for the synthesis of strating that looping of distal enhancers to their target promoters is functional proteins, while the remaining 98–99% gives rise to a required for enhancer function (reviewed in ref. 22). For example, plethora of ncRNAs, including transfer RNAs (tRNAs), ribosomal a key study revealed that experimental induction of chromatin RNAs (rRNAs), intronic RNAs, small nuclear (sn)RNAs, small looping between the mouse β-globin (Hbb) promoter and its asso- nucleolar (sno)RNAs, microRNAs (miRNAs) and long noncoding ciated enhancer region results in transcriptional activation of the RNAs (lncRNAs). A recent addition to the expanding list of regu- Hbb gene23.