BAZ2A safeguards genome architecture of ground-state pluripotent stem cells.
BAZ2A safeguards genome architecture of ground-state pluripotent stem cells.
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DOI：
10.15252/embj.2020105606
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发表时间：
2020-12-01
期刊：
影响因子：
--
通讯作者：
Santoro R
中科院分区：
文献类型：
--
作者：
Dalcher D;Tan JY;Bersaglieri C;Peña-Hernández R;Vollenweider E;Zeyen S;Schmid MW;Bianchi V;Butz S;Roganowicz M;Kuzyakiv R;Baubec T;Marques AC;Santoro R
染色体具有分离成区室的内在倾向，在相似染色质状态的基因座之间形成长距离接触。基因组区室化是如何调控的仍然是难以捉摸的。在这里，以开放和活性染色质为特征的小鼠基态胚胎干细胞（ESC）与具有更封闭和抑制的基因组的晚期血清ESC的比较揭示了由于对BAZ 2A/TIP 5（染色质重塑复合物NoRC的一种组分）的差异依赖性而对其基因组组织的不同调节。在ESC染色质上，BAZ 2A与SNF 2 H、DNA拓扑异构酶2A（TOP 2A）和粘附素相互作用。BAZ 2A与活性A区室内的染色质亚结构域相关联，其通过长距离接触相交。我们发现，基态染色质选择性地需要BAZ 2A来限制活性结构域侵入抑制区室。BAZ 2A耗竭增加了B区室的染色质可及性。此外，BAZ 2A以TOP 2A依赖性方式调节H3 K27 me 3基因组占有率。最后，基态ESC需要BAZ 2A来生长、分化和正确表达发育基因。我们的研究结果揭示了开放的染色质结构域侵入抑制性结构域的倾向，这被染色质重塑所抵消，以建立基因组分区并保持细胞身份。NoRC染色质重塑亚基BAZ 2A限制活性染色质区室并确保ESC中的发育基因表达。
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 serum ESCs with a more closed and repressed genome, reveals distinct regulation of their genome organization due to differential dependency on BAZ2A/TIP5, a component of the chromatin remodeling complex NoRC. On ESC chromatin, BAZ2A interacts with SNF2H, DNA topoisomerase 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 requires BAZ2A 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 a TOP2A‐dependent manner. Finally, ground‐state ESCs require BAZ2A 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. The NoRC chromatin remodeller subunit BAZ2A restricts active chromatin compartments and secures developmental gene expression in ESCs.
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影响因子：
21.3
作者：
Boroviak T;Loos R;Bertone P;Smith A;Nichols J
通讯作者：
Nichols J
影响因子：
16.8
作者：
Leitch, Harry G.;McEwen, Kirsten R.;Turp, Aleksandra;Encheva, Vesela;Carroll, Tom;Grabole, Nils;Mansfield, William;Nashun, Buhe;Knezovich, Jaysen G.;Smith, Austin;Surani, M. Azim;Hajkova, Petra
通讯作者：
Hajkova, Petra
影响因子：
64.5
作者：
Haarhuis JHI;van der Weide RH;Blomen VA;Yáñez-Cuna JO;Amendola M;van Ruiten MS;Krijger PHL;Teunissen H;Medema RH;van Steensel B;Brummelkamp TR;de Wit E;Rowland BD
通讯作者：
Rowland BD
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
64.8
作者：
Cabianca, Daphne S.;Munoz-Jimenez, Celia;Gasser, Susan M.
通讯作者：
Gasser, Susan M.