BAZ2A safeguards genome architecture of ground-state pluripotent stem cells

被引：17

作者：

Dalcher, Damian ^{[1
,2
]}

Tan, Jennifer Yihong ^{[3
]}

Bersaglieri, Cristiana ^{[1
,2
]}

Pena-Hernandez, Rodrigo ^{[1
,2
]}

Vollenweider, Eva ^{[1
,2
]}

Zeyen, Stefan ^{[1
,2
]}

Schmid, Marc W. ^{[4
]}

Bianchi, Valerio ^{[5
]}

Butz, Stefan ^{[1
,2
]}

Roganowicz, Marcin ^{[1
,2
]}

Kuzyakiv, Rostyslav ^{[1
,4
]}

Baubec, Tuncay ^{[1
]}

Marques, Ana Claudia ^{[3
]}

Santoro, Raffaella ^{[1
]}

机构：

[1] Univ Zurich, Dept Mol Mech Dis, DMMD, Zurich, Switzerland

[2] Univ Zurich, Life Sci Zurich Grad Sch, Mol Life Sci Program, Zurich, Switzerland

[3] Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland

[4] Univ Zurich, Serv & Support Sci IT, Zurich, Switzerland

[5] Univ Med Ctr Utrecht, Oncode Inst, Hubrecht Inst KNAW, Utrecht, Netherlands

来源：

EMBO JOURNAL | 2020年 / 39卷 / 23期

基金：

瑞士国家科学基金会;

关键词：

BAZ2A; genome organization; ground-state embryonic stem cells; Topoisomerase; 2A; DNA TOPOISOMERASE-II; HETEROCHROMATIN FORMATION; GENE-EXPRESSION; READ ALIGNMENT; CHROMATIN; REORGANIZATION; RESOLUTION; PRINCIPLES; NORC; ACCURATE;

D O I：

10.15252/embj.2020105606

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Chromosomes have an intrinsic tendency to segregate into compartments, forming long-distance contacts between loci of similar chromatin states. How genome compartmentalization is regulated remains elusive. Here, comparison of mouse ground-state embryonic stem cells (ESCs) characterized by open and active chromatin, and advanced serumESCs with a more closed and repressed genome, reveals distinct regulation of their genome organization due to differential dependency onBAZ2A/TIP5, a component of the chromatin remodeling complex NoRC. OnESCchromatin,BAZ2A interacts withSNF2H,DNAtopoisomerase 2A (TOP2A) and cohesin.BAZ2A associates with chromatin sub-domains within the active A compartment, which intersect through long-range contacts. We found that ground-state chromatin selectively requiresBAZ2A to limit the invasion of active domains into repressive compartments.BAZ2A depletion increases chromatin accessibility at B compartments. Furthermore,BAZ2A regulates H3K27me3 genome occupancy in aTOP2A-dependent manner. Finally, ground-stateESCs requireBAZ2A for growth, differentiation, and correct expression of developmental genes. Our results uncover the propensity of open chromatin domains to invade repressive domains, which is counteracted by chromatin remodeling to establish genome partitioning and preserve cell identity.

引用

页数：23

共 65 条

[11] Control of Cell Identity Genes Occurs in Insulated Neighborhoods in Mammalian Chromosomes [J].

Dowen, Jill M. ;

Fan, Zi Peng ;

Hnisz, Denes ;

Ren, Gang ;

Abraham, Brian J. ;

Zhang, Lyndon N. ;

Weintraub, Abraham S. ;

Schuijers, Jurian ;

Lee, Tong Ihn ;

Zhao, Keji ;

Young, Richard A. .

CELL, 2014, 159 (02) :374-387

[12] Juicer Provides a One-Click System for Analyzing Loop-Resolution Hi-C Experiments [J].

Durand, Neva C. ;

Shamim, Muhammad S. ;

Machol, Ido ;

Rao, Suhas S. P. ;

Huntley, Miriam H. ;

Lander, Eric S. ;

Aiden, Erez Lieberman .

CELL SYSTEMS, 2016, 3 (01) :95-98

[13] BAF complexes facilitate decatenation of DNA by topoisomerase IIα [J].

Dykhuizen, Emily C. ;

Hargreaves, Diana C. ;

Miller, Erik L. ;

Cui, Kairong ;

Korshunov, Andrey ;

Kool, Marcel ;

Pfister, Stefan ;

Cho, Yoon-Jae ;

Zhao, Keji ;

Crabtree, Gerald R. .

NATURE, 2013, 497 (7451) :624-+

[14] FGF Signaling Inhibition in ESCs Drives Rapid Genome-wide Demethylation to the Epigenetic Ground State of Pluripotency [J].

Ficz, Gabriella ;

Hore, Timothy A. ;

Santos, Fatima ;

Lee, Heather J. ;

Dean, Wendy ;

Arand, Julia ;

Krueger, Felix ;

Oxley, David ;

Paul, Yu-Lee ;

Walter, Joern ;

Cook, Simon J. ;

Andrews, Simon ;

Branco, Miguel R. ;

Reik, Wolf .

CELL STEM CELL, 2013, 13 (03) :351-359

[15] Inheritance of Silent rDNA Chromatin Is Mediated by PARP1 via Noncoding RNA [J].

Guetg, Claudio ;

Scheifele, Fabian ;

Rosenthal, Florian ;

Hottiger, Michael O. ;

Santoro, Raffaella .

MOLECULAR CELL, 2012, 45 (06) :790-800

[16] The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats [J].

Guetg, Claudio ;

Lienemann, Philipp ;

Sirri, Valentina ;

Grummt, Ingrid ;

Hernandez-Verdun, Daniele ;

Hottiger, Michael O. ;

Fussenegger, Martin ;

Santoro, Raffaella .

EMBO JOURNAL, 2010, 29 (13) :2135-2146

[17] The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension [J].

Haarhuis, Judith H. I. ;

van der Weide, Robin H. ;

Blomen, Vincent A. ;

Yanez-Cuna, J. Omar ;

Amendola, Mario ;

van Ruiten, Marjon S. ;

Krijger, Peter H. L. ;

Teunissen, Hans ;

Medema, Rene H. ;

van Steensel, Bas ;

Brummelkamp, Thijn R. ;

de Wit, Elzo ;

Rowland, Benjamin D. .

CELL, 2017, 169 (04) :693-707

[18] Whole-Genome Bisulfite Sequencing of Two Distinct Interconvertible DNA Methylomes of Mouse Embryonic Stem Cells [J].

Habibi, Ehsan ;

Brinkman, Arie B. ;

Arand, Julia ;

Kroeze, Leonie I. ;

Kerstens, Hindrik H. D. ;

Matarese, Filomena ;

Lepikhov, Konstantin ;

Gut, Marta ;

Brun-Heath, Isabelle ;

Hubner, Nina C. ;

Benedetti, Rosaria ;

Altucci, Lucia ;

Jansen, Joop H. ;

Walter, Joern ;

Gut, Ivo G. ;

Marks, Hendrik ;

Stunnenberg, Hendrik G. .

CELL STEM CELL, 2013, 13 (03) :360-369

[19] Regulatory Principles of Pluripotency: From the Ground State Up [J].

Hackett, Jamie A. ;

Surani, M. Azim .

CELL STEM CELL, 2014, 15 (04) :416-430

[20] GAT: a simulation framework for testing the association of genomic intervals [J].

Heger, Andreas ;

Webber, Caleb ;

Goodson, Martin ;

Ponting, Chris P. ;

Lunter, Gerton .

BIOINFORMATICS, 2013, 29 (16) :2046-2048

← 1 2 3 4 5 6 7 →