Gene Expression Changes During Retinal Development and Rod Specification
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A Prelude to the Proximity Interaction Mapping of CXXC5
www.nature.com/scientificreports OPEN A prelude to the proximity interaction mapping of CXXC5 Gamze Ayaz1,4,6*, Gizem Turan1,6, Çağla Ece Olgun1,6, Gizem Kars1, Burcu Karakaya1, Kerim Yavuz1, Öykü Deniz Demiralay1, Tolga Can2, Mesut Muyan1,3* & Pelin Yaşar1,5,6 CXXC5 is a member of the zinc-fnger CXXC family proteins that interact with unmodifed CpG dinucleotides through a conserved ZF-CXXC domain. CXXC5 is involved in the modulation of gene expressions that lead to alterations in diverse cellular events. However, the underlying mechanism of CXXC5-modulated gene expressions remains unclear. Proteins perform their functions in a network of proteins whose identities and amounts change spatiotemporally in response to various stimuli in a lineage-specifc manner. Since CXXC5 lacks an intrinsic transcription regulatory function or enzymatic activity but is a DNA binder, CXXC5 by interacting with proteins could act as a scafold to establish a chromatin state restrictive or permissive for transcription. To initially address this, we utilized the proximity-dependent biotinylation approach. Proximity interaction partners of CXXC5 include DNA and chromatin modifers, transcription factors/co-regulators, and RNA processors. Of these, CXXC5 through its CXXC domain interacted with EMD, MAZ, and MeCP2. Furthermore, an interplay between CXXC5 and MeCP2 was critical for a subset of CXXC5 target gene expressions. It appears that CXXC5 may act as a nucleation factor in modulating gene expressions. Providing a prelude for CXXC5 actions, our results could also contribute to a better understanding of CXXC5-mediated cellular processes in physiology and pathophysiology. Te methylation of mammalian genomic DNA, which predominantly arises post-replicatively at the 5’ posi- tion of the cytosine base in the context of CpG dinucleotides, varies across cell types, developmental stages, physiological and pathophysiological conditions 1. -
Open Dogan Phdthesis Final.Pdf
The Pennsylvania State University The Graduate School Eberly College of Science ELUCIDATING BIOLOGICAL FUNCTION OF GENOMIC DNA WITH ROBUST SIGNALS OF BIOCHEMICAL ACTIVITY: INTEGRATIVE GENOME-WIDE STUDIES OF ENHANCERS A Dissertation in Biochemistry, Microbiology and Molecular Biology by Nergiz Dogan © 2014 Nergiz Dogan Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy August 2014 ii The dissertation of Nergiz Dogan was reviewed and approved* by the following: Ross C. Hardison T. Ming Chu Professor of Biochemistry and Molecular Biology Dissertation Advisor Chair of Committee David S. Gilmour Professor of Molecular and Cell Biology Anton Nekrutenko Professor of Biochemistry and Molecular Biology Robert F. Paulson Professor of Veterinary and Biomedical Sciences Philip Reno Assistant Professor of Antropology Scott B. Selleck Professor and Head of the Department of Biochemistry and Molecular Biology *Signatures are on file in the Graduate School iii ABSTRACT Genome-wide measurements of epigenetic features such as histone modifications, occupancy by transcription factors and coactivators provide the opportunity to understand more globally how genes are regulated. While much effort is being put into integrating the marks from various combinations of features, the contribution of each feature to accuracy of enhancer prediction is not known. We began with predictions of 4,915 candidate erythroid enhancers based on genomic occupancy by TAL1, a key hematopoietic transcription factor that is strongly associated with gene induction in erythroid cells. Seventy of these DNA segments occupied by TAL1 (TAL1 OSs) were tested by transient transfections of cultured hematopoietic cells, and 56% of these were active as enhancers. Sixty-six TAL1 OSs were evaluated in transgenic mouse embryos, and 65% of these were active enhancers in various tissues. -
Evaluation of Chromatin Accessibility in Prefrontal Cortex of Individuals with Schizophrenia
ARTICLE DOI: 10.1038/s41467-018-05379-y OPEN Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia Julien Bryois 1, Melanie E. Garrett2, Lingyun Song3, Alexias Safi3, Paola Giusti-Rodriguez 4, Graham D. Johnson 3, Annie W. Shieh13, Alfonso Buil5, John F. Fullard6, Panos Roussos 6,7,8, Pamela Sklar6, Schahram Akbarian 6, Vahram Haroutunian 6,9, Craig A. Stockmeier 10, Gregory A. Wray3,11, Kevin P. White12, Chunyu Liu13, Timothy E. Reddy 3,14, Allison Ashley-Koch2,15, Patrick F. Sullivan 1,4,16 & Gregory E. Crawford 3,17 1234567890():,; Schizophrenia genome-wide association studies have identified >150 regions of the genome associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore the mechanism of non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals with schizophrenia and 137 controls, and identified 118,152 ATAC-seq peaks. These accessible chromatin regions in the brain are highly enriched for schizophrenia SNP heritability. Accessible chromatin regions that overlap evolutionarily conserved regions exhibit an even higher heritability enrichment, indicating that sequence conservation can further refine functional risk variants. We identify few differences in chromatin accessibility between cases and controls, in contrast to thousands of age-related differential accessible chromatin regions. Altogether, we characterize chromatin accessibility in the human prefrontal cortex, the effect of schizophrenia and age on chromatin accessibility, and provide evidence that our dataset will allow for fine mapping of risk variants. 1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177 Stockholm, Sweden. -
3398 Orphan Nuclear Receptor Function in the Ovary Huajun Zhao1, Zili
[Frontiers in Bioscience 12, 3398-3405, May 1, 2007] Orphan nuclear receptor function in the ovary Huajun Zhao1, Zili Li1, Austin J. Cooney2, Zi-Jian Lan1 1Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY 40202 2Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Germ Cell Nuclear Factor 4. Steroidogenic Factor-1 5. Liver Receptor Homolog-1 6. Perspective 7. Acknowledgement 8. References 1. ABSTRACT 2. INTRODUCTION Orphan nuclear receptors such as germ cell In the mammalian ovary, follicles are the nuclear factor (GCNF), steroidogenic factor 1 (SF-1) and principal functional units which provide the support system liver receptor homolog-1 (LRH-1), are emerging as necessary for production of female germ cells (mature important ovarian factors in regulating female oocytes) during postnatal life (1). The process of follicular reproduction. Within the ovary, GCNF (NR6A1) development after birth is termed folliculogenesis and the expression is restricted to the oocyte, while SF-1 (NR5A1) production of fertilizable eggs is referred to as oogenesis. is expressed only in the somatic cells, such as granulosa, During reproductive life, folliculogenesis and oogenesis are thecal and luteal cells, and interstitial cells. LRH-1 highly coordinated to ensure the production of fertilizable (NR5A2), an orphan receptor closely related to SF-1, is eggs. These processes require intercellular communication expressed only in the granulosa cells of the follicles and between many cell types such as oocytes, granulosa and luteal cells within the ovary. Recent studies using thecal cells within the ovary (2, 3). -
The Function of NFIX During Developmental and Adult Neurogenesis
The function of NFIX during developmental and adult neurogenesis Lachlan Ian Harris Bachelor of Science (Biomedical), Honours Class I A thesis submitted for the degree of Doctor of Philosophy at The University of Queensland in 2017 Faculty of Medicine 1 Abstract Understanding the transcription factor proteins that control the biology of neural stem cells during embryogenesis provides insight into brain development as well as neurodevelopmental disorders. Likewise, studying the function of transcription factors in adult neural stem cells allows us to appreciate the dynamics of these cells and their contribution to normal cognitive function. It also provides a knowledge base so as to one day harness the activity of adult neural stem cells to treat degenerative conditions of the nervous system. One family of transcription factors key to brain development are the Nuclear Factor Ones (NFIs). Comprised of four members in mammals (NFIA, NFIB, NFIC and NFIX) these proteins promote both neuronal and glial differentiation during mouse forebrain development, and in general, appear to have a highly similar function. This thesis addressed two outstanding questions regarding the function of one these proteins, NFIX, in mouse neural stem cell biology. The first question concerned refining our understanding of NFIX function during forebrain development by determining, which stage of neuron differentiation, from a stem cell to a mature neuron, is controlled by NFIX? I answered this question by studying early changes in progenitor populations in loss-of-function mice, revealing that NFIX promotes the production of intermediate neuronal progenitors by directing stem cells to divide in an asymmetric manner. Mechanistically, this was because NFIX, and NFIA/B activated the expression of the spindle regulator Inscuteable, which changes cleavage plane orientations to direct an intermediate neuronal progenitor cell fate. -
(12) Patent Application Publication (10) Pub. No.: US 2003/0082511 A1 Brown Et Al
US 20030082511A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0082511 A1 Brown et al. (43) Pub. Date: May 1, 2003 (54) IDENTIFICATION OF MODULATORY Publication Classification MOLECULES USING INDUCIBLE PROMOTERS (51) Int. Cl." ............................... C12O 1/00; C12O 1/68 (52) U.S. Cl. ..................................................... 435/4; 435/6 (76) Inventors: Steven J. Brown, San Diego, CA (US); Damien J. Dunnington, San Diego, CA (US); Imran Clark, San Diego, CA (57) ABSTRACT (US) Correspondence Address: Methods for identifying an ion channel modulator, a target David B. Waller & Associates membrane receptor modulator molecule, and other modula 5677 Oberlin Drive tory molecules are disclosed, as well as cells and vectors for Suit 214 use in those methods. A polynucleotide encoding target is San Diego, CA 92121 (US) provided in a cell under control of an inducible promoter, and candidate modulatory molecules are contacted with the (21) Appl. No.: 09/965,201 cell after induction of the promoter to ascertain whether a change in a measurable physiological parameter occurs as a (22) Filed: Sep. 25, 2001 result of the candidate modulatory molecule. Patent Application Publication May 1, 2003 Sheet 1 of 8 US 2003/0082511 A1 KCNC1 cDNA F.G. 1 Patent Application Publication May 1, 2003 Sheet 2 of 8 US 2003/0082511 A1 49 - -9 G C EH H EH N t R M h so as se W M M MP N FIG.2 Patent Application Publication May 1, 2003 Sheet 3 of 8 US 2003/0082511 A1 FG. 3 Patent Application Publication May 1, 2003 Sheet 4 of 8 US 2003/0082511 A1 KCNC1 ITREXCHO KC 150 mM KC 2000000 so 100 mM induced Uninduced Steady state O 100 200 300 400 500 600 700 Time (seconds) FIG. -
Independent Regulation of Vertebral Number and Vertebral Identity by Microrna-196 Paralogs
Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs Siew Fen Lisa Wonga,1, Vikram Agarwalb,c,d,e,1, Jennifer H. Mansfieldf,g, Nicolas Denansh, Matthew G. Schwartzf, Haydn M. Prosseri, Olivier Pourquiéf,j, David P. Bartelb,c,d, Clifford J. Tabinf,2, and Edwina McGlinna,f,2 aEMBL Australia, Australian Regenerative Medicine Institute, Monash University, Clayton, VIC 3800, Australia; bHoward Hughes Medical Institute, Cambridge, MA 02142; cWhitehead Institute for Biomedical Research, Cambridge, MA 02142; dDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; eComputational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139; fDepartment of Genetics, Harvard Medical School, Boston, MA 02115; gDepartment of Biological Sciences, Barnard College, New York, NY 10027; hDepartment of Developmental Biology and Genetics, Stanford School of Medicine, Stanford, CA 94305; iThe Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom; and jDepartment of Pathology, Brigham and Women’s Hospital, Boston, MA 02115 Contributed by Clifford J. Tabin, July 16, 2015 (sent for review March 24, 2015; reviewed by Jacqueline Deschamps and Joshua T. Mendell) The Hox genes play a central role in patterning the embryonic anterior- of which is a critical factor in establishing species-specific vertebral to-posterior axis. An important function of Hox activity in verte- number (8). brates is the specification of different vertebral morphologies, with Within vertebral precursors, specific combinations of Hox an additional role in axis elongation emerging. The miR-196 family transcription factors impart positional information that governs of microRNAs (miRNAs) are predicted to extensively target Hox 3′ vertebral identity (9). -
Strategies to Study Sex-Determining Genes in the Mouse
Strategies to study sex-determining genes in the mouse Amy E. Johnson A thesis submitted to the University of London in fulfilment of the requirements for the degree of Doctor of Philosophy. May 2002 Division of Developmental Genetics, National Institute For Medical Research, The Ridgeway, Mill Hill, London, NW7 lAY. ProQuest Number: U643301 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U643301 Published by ProQuest LLC(2015). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 This thesis is dedicated to my immediate family, Janice, Clive, Molly, Matthew, Ben, Emma and my fiancé Geoff Table Of Contents ACKNOWLEDGEMENTS ............................................ / ABSTRACT ....................................................................................................................IV 1 CHAPTER 1- GENERAL INTRODUCTION....................................................... 1 lA SEX DETERMINATION......................................................................................1 1.1.1 Drosophila and C-ele^ans .................................................................................1 -
Testing a Mesendoderm Protocol in Smad5 and Smad1/5 Depleted Embryonic Stem Cells for Primordial Germ Cell Induction
UNIVERSIDADE DE LISBOA FACULDADE DE CIÊNCIAS DEPARTAMENTO DE BIOLOGIA ANIMAL Testing a mesendoderm protocol in Smad5 and Smad1/5 depleted embryonic stem cells for primordial germ cell induction Mestrado em Biologia Evolutiva e do Desenvolvimento Sara Mariana Eugénio Ferraz Mendes Dissertação orientada por: Professora Dra. Susana Marina Chuva de Sousa Lopes e Professora Dra. Maria Gabriela Rodrigues 2015 Contents i. Acknowledgements ................................................................................................................................ I ii. Abbreviations .................................................................................................................................... II iii. Abstract ............................................................................................................................................ III iv. Resumo ............................................................................................................................................ IV I. Introduction .............................................................................................................................. 1 1. Embryonic Stem Cells in mouse ............................................................................................ 2 2. BMP signalling: BMP4 and Smads 1/5 .................................................................................. 3 3. Primordial germ cells (PGCS)................................................................................................ -
Table SII. Significantly Differentially Expressed Mrnas of GSE23558 Data Series with the Criteria of Adjusted P<0.05 And
Table SII. Significantly differentially expressed mRNAs of GSE23558 data series with the criteria of adjusted P<0.05 and logFC>1.5. Probe ID Adjusted P-value logFC Gene symbol Gene title A_23_P157793 1.52x10-5 6.91 CA9 carbonic anhydrase 9 A_23_P161698 1.14x10-4 5.86 MMP3 matrix metallopeptidase 3 A_23_P25150 1.49x10-9 5.67 HOXC9 homeobox C9 A_23_P13094 3.26x10-4 5.56 MMP10 matrix metallopeptidase 10 A_23_P48570 2.36x10-5 5.48 DHRS2 dehydrogenase A_23_P125278 3.03x10-3 5.40 CXCL11 C-X-C motif chemokine ligand 11 A_23_P321501 1.63x10-5 5.38 DHRS2 dehydrogenase A_23_P431388 2.27x10-6 5.33 SPOCD1 SPOC domain containing 1 A_24_P20607 5.13x10-4 5.32 CXCL11 C-X-C motif chemokine ligand 11 A_24_P11061 3.70x10-3 5.30 CSAG1 chondrosarcoma associated gene 1 A_23_P87700 1.03x10-4 5.25 MFAP5 microfibrillar associated protein 5 A_23_P150979 1.81x10-2 5.25 MUCL1 mucin like 1 A_23_P1691 2.71x10-8 5.12 MMP1 matrix metallopeptidase 1 A_23_P350005 2.53x10-4 5.12 TRIML2 tripartite motif family like 2 A_24_P303091 1.23x10-3 4.99 CXCL10 C-X-C motif chemokine ligand 10 A_24_P923612 1.60x10-5 4.95 PTHLH parathyroid hormone like hormone A_23_P7313 6.03x10-5 4.94 SPP1 secreted phosphoprotein 1 A_23_P122924 2.45x10-8 4.93 INHBA inhibin A subunit A_32_P155460 6.56x10-3 4.91 PICSAR P38 inhibited cutaneous squamous cell carcinoma associated lincRNA A_24_P686965 8.75x10-7 4.82 SH2D5 SH2 domain containing 5 A_23_P105475 7.74x10-3 4.70 SLCO1B3 solute carrier organic anion transporter family member 1B3 A_24_P85099 4.82x10-5 4.67 HMGA2 high mobility group AT-hook 2 A_24_P101651 -
Detection of Differentially Methylated Regions Using Bayes Factor For
G C A T T A C G G C A T genes Article Detection of Differentially Methylated Regions Using Bayes Factor for Ordinal Group Responses Fengjiao Dunbar 1, Hongyan Xu 2, Duchwan Ryu 3, Santu Ghosh 2, Huidong Shi 4 and Varghese George 2,* 1 Genomics Research Center, AbbVie, North Chicago, IL 60064, USA; [email protected] 2 Department of Population Health Sciences, Augusta University, Augusta, GA 30912, USA; [email protected] (H.X.); [email protected] (S.G.) 3 Department of Statistics and Actuarial Science, Northern Illinois University, DeKalb, IL 60178, USA; [email protected] 4 Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-706-721-0801 Received: 19 July 2019; Accepted: 15 September 2019; Published: 17 September 2019 Abstract: Researchers in genomics are increasingly interested in epigenetic factors such as DNA methylation, because they play an important role in regulating gene expression without changes in the DNA sequence. There have been significant advances in developing statistical methods to detect differentially methylated regions (DMRs) associated with binary disease status. Most of these methods are being developed for detecting differential methylation rates between cases and controls. We consider multiple severity levels of disease, and develop a Bayesian statistical method to detect the region with increasing (or decreasing) methylation rates as the disease severity increases. Patients are classified into more than two groups, based on the disease severity (e.g., stages of cancer), and DMRs are detected by using moving windows along the genome. Within each window, the Bayes factor is calculated to test the hypothesis of monotonic increase in methylation rates corresponding to severity of the disease versus no difference. -
“The Transcription Factor NFIX As a Novel Modulator of Heart Rate.”
PhD course of Integrated Biomedical Research Cycle XXXI BIO-09 “The transcription factor NFIX as a novel modulator of heart rate.” Sara Landi R11322 Tutor: Prof. Andrea Francesco Barbuti PhD Course Coordinator: Prof. Chiarella Sforza 2017/2018 1 Summary Abstract .................................................................................................. 4 Introduction .......................................................................................... 6 1. The transcription factor NFIX. ........................................................ 6 2. Heart development. ........................................................................ 13 3. The Heart. ...................................................................................... 18 I. The Working Myocardium. ......................................................... 18 II. The Conduction System .............................................................. 18 4. The Cardiac Action Potential. ........................................................ 24 5. HCN Channels. .............................................................................. 27 6. L-type Calcium Channels. .............................................................. 32 Aim ......................................................................................................... 37 Materials and methods ..................................................................... 38 1. Statistical Analysis ......................................................................... 38 2. Mouse model .................................................................................