Tet2 regulates Sin3a recruitment at active enhancers in embryonic stem cells.
Tet2 regulates Sin3a recruitment at active enhancers in embryonic stem cells.
复制标题
TET2调节胚胎干细胞中活性增强子的SIN3A募集。
DOI：
10.1016/j.isci.2023.107170
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发表时间：
2023-07-21
期刊：
影响因子：
5.8
通讯作者：
Dawlaty, Meelad M.
中科院分区：
文献类型：
--
作者：
Flores, Julio C.;Sidoli, Simone;Dawlaty, Meelad M.
TET2是Ten-Eleven易位(Tet1/2/3)家族的成员，在胚胎干细胞(ESCs)中表达。它使DNA去甲基化(催化功能)，并与染色质修饰剂(非催化功能)合作来调节基因。然而，这些功能在ESCs中的意义还不是很清楚。利用TET2催化突变体(Tet2m/m)和敲除(Tet2−/−)ESCs，我们鉴定了TET2受其催化依赖和独立作用调控的靶基因。TET2在其活性增强剂和启动子中被富含，以使其去甲基化。我们还确定组蛋白脱乙酰酶成分Sin3a是TET2的合作伙伴，共同定位于启动子和活性增强子。TET2缺乏使这些区域的SIN3a减少。TET2和Sin3a与Tet1重叠。Tet1/2的联合缺失，但不是它们的催化活性的丧失，降低了活性增强剂上的Sin3a。这些发现确立了TET2的催化和非催化功能，作为DNA去甲基化和SIN3a在ESCs的活性增强子上的募集的调节。TET2在ESCs中有不同的催化和非催化靶基因TET2去甲基化其靶基因TET2和Sin3a的增强子和启动子在ESCs中相互作用并共占活性增强剂TET2非催化促进Sin3a在活性增强剂上的浓缩生物科学；遗传学；分子生物学
Tet2 is a member of the Ten-eleven translocation (Tet1/2/3) family of enzymes and is expressed in embryonic stem cells (ESCs). It demethylates DNA (catalytic functions) and partners with chromatin modifiers (noncatalytic functions) to regulate genes. However, the significance of these functions in ESCs is less defined. Using Tet2 catalytic mutant (Tet2m/m) and knockout (Tet2−/−) ESCs, we identified Tet2 target genes regulated by its catalytic dependent versus independent roles. Tet2 was enriched at their active enhancers and promoters to demethylate them. We also identified the histone deacetylase component Sin3a as a Tet2 partner, co-localizing at promoters and active enhancers. Tet2 deficiency diminished Sin3a at these regions. Tet2 and Sin3a co-occupancy overlapped with Tet1. Combined loss of Tet1/2, but not of their catalytic activities, reduced Sin3a at active enhancers. These findings establish Tet2 catalytic and noncatalytic functions as regulators of DNA demethylation and Sin3a recruitment at active enhancers in ESCs. Tet2 has distinct catalytic and noncatalytic target genes in ESCs Tet2 demethylates enhancers and promoters of its target genes Tet2 and Sin3a interact in ESCs and co-occupy active enhancers Tet2 noncatalytically facilitates Sin3a enrichment at active enhancers Biological sciences; Genetics; Molecular biology
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影响因子：
23.9
作者：
Dawlaty, Meelad M.;Ganz, Kibibi;Powell, Benjamin E.;Hu, Yueh-Chiang;Markoulaki, Styliani;Cheng, Albert W.;Gao, Qing;Kim, Jongpil;Choi, Sang-Woon;Page, David C.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
8.8
作者：
Ito, Kyoko;Lee, Joun;Ito, Keisuke
通讯作者：
Ito, Keisuke
影响因子：
11.8
作者：
Dawlaty, Meelad M.;Breiling, Achim;Le, Thuc;Raddatz, Guenter;Barrasa, M. Inmaculada;Cheng, Albert W.;Gao, Qing;Powell, Benjamin E.;Li, Zhe;Xu, Mingjiang;Faull, Kym F.;Lyko, Frank;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
4.6
作者：
Chandru A;Bate N;Vuister GW;Cowley SM
通讯作者：
Cowley SM
影响因子：
30.8
作者：
Guallar D;Bi X;Pardavila JA;Huang X;Saenz C;Shi X;Zhou H;Faiola F;Ding J;Haruehanroengra P;Yang F;Li D;Sanchez-Priego C;Saunders A;Pan F;Valdes VJ;Kelley K;Blanco MG;Chen L;Wang H;Sheng J;Xu M;Fidalgo M;Shen X;Wang J
通讯作者：
Wang J