Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb16.
Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb16.
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DOI：
10.1038/s41590-018-0238-4
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发表时间：
2018-12
影响因子：
30.5
通讯作者：
Rothenberg EV
中科院分区：
文献类型：
--
作者：
Hosokawa H;Romero-Wolf M;Yui MA;Ungerbäck J;Quiloan MLG;Matsumoto M;Nakayama KI;Tanaka T;Rothenberg EV
多能祖细胞在DN 2 pro-T细胞阶段确认其T细胞谱系身份，此时开始表达必需的转录因子Bcl 11b。在体内和体外阶段特异性删除全球确定Bcl 11 b控制的靶基因在pro-T细胞。蛋白质组学分析表明，Bcl 11b与多种辅助因子，它的直接行动是需要招募这些辅助因子的选择性靶位点。这些网站的Bcl 11b依赖辅因子的招聘富集功能调节的靶基因附近，和个别辅因子的删除解除了许多Bcl 11b阻遏基因的阻遏。Runx 1与Bcl 11b最常合作激活和抑制。与此同时，Bcl 11b通过基因网络电路通过Id 2和Zbtb 16（编码PLZF）间接调节靶基因的一个子集，这些基因被Bcl 11b直接抑制并控制不同的替代程序。因此，这项研究定义了直接和间接Bcl 11b行动，促进T细胞的身份和阻断替代电位的分子基础。
Multipotent progenitors confirm their T cell-lineage identity in the DN2 pro-T cell stages, when expression of the essential transcription factor Bcl11b begins. In vivo and in vitro stage-specific deletions globally identified Bcl11b-controlled target genes in pro-T cells. Proteomic analysis revealed that Bcl11b associates with multiple cofactors, and that its direct action was needed to recruit these cofactors to selective target sites. These sites of Bcl11b-dependent cofactor recruitment were enriched near functionally regulated target genes, and deletion of individual cofactors relieved repression of many Bcl11b-repressed genes. Runx1 collaborated with Bcl11b most frequently for both activation and repression. In parallel, Bcl11b indirectly regulated a subset of target genes by a gene network circuit via Id2 and Zbtb16 (encoding PLZF), which were directly repressed by Bcl11b and controlled distinct alternative programs. Thus, this study defines the molecular basis of direct and indirect Bcl11b actions that promote T cell identity and block alternative potentials.
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影响因子：
32.4
作者：
Hu G;Cui K;Fang D;Hirose S;Wang X;Wangsa D;Jin W;Ried T;Liu P;Zhu J;Rothenberg EV;Zhao K
通讯作者：
Zhao K
影响因子：
10.5
作者：
Champhekar A;Damle SS;Freedman G;Carotta S;Nutt SL;Rothenberg EV
通讯作者：
Rothenberg EV
影响因子：
32.4
作者：
Califano D;Cho JJ;Uddin MN;Lorentsen KJ;Yang Q;Bhandoola A;Li H;Avram D
通讯作者：
Avram D
影响因子：
30.5
作者：
Ishizuka IE;Chea S;Gudjonson H;Constantinides MG;Dinner AR;Bendelac A;Golub R
通讯作者：
Golub R
DOI：
10.1073/pnas.1423244112
发表时间：
2015-04-21
影响因子：
11.1
作者：
Constantinides, Michael G.;Gudjonson, Herman;Bendelac, Albert
通讯作者：
Bendelac, Albert