Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities.
Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities.
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DOI：
10.1016/j.molcel.2010.05.004
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发表时间：
2010-05-28
期刊：
影响因子：
16
通讯作者：
Glass CK
中科院分区：
文献类型：
--
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
基因组规模的研究已经揭示了广泛的，细胞类型特异性的转录因子共定位，但这种现象背后的机制仍然知之甚少。在这里，我们证明了在巨噬细胞和B细胞的共同因子PU.1与巨噬细胞或B细胞系决定转录因子的小集合的协作相互作用建立与大多数启动子远端H3K4me1标记的基因组区域相关的细胞特异性结合位点。PU.1结合启动核小体重塑，随后在与广泛和特异表达的基因相关的大量基因组区域发生H3K4单甲基化。这些位置可以作为其他因素的信标，例如肝脏X受体，它驱动细胞特异性基因表达和信号依赖性反应。结合其他细胞类型中的转录因子结合和H3K4me1模式的分析，这些研究表明，谱系决定转录因子的简单组合可以指定最终负责细胞身份和细胞类型特异性反应的基因组位点。
Genome-scale studies have revealed extensive, cell type-specific co-localization of transcription factors, but the mechanisms underlying this phenomenon remain poorly understood. Here we demonstrate in macrophages and B cells that collaborative interactions of the common factor PU.1 with small sets of macrophage- or B celllineage-determining transcription factors establish cell-specific binding sites that are associated with the majority of promoter-distal H3K4me1-marked genomic regions. PU.1 binding initiates nucleosome remodeling followed by H3K4 monomethylation at large numbers of genomic regions associated with both broadly and specifically expressed genes. These locations serve as beacons for additional factors, exemplified by liver X receptors, which drive both cell-specific gene expression and signal-dependent responses. Together with analyses of transcription factor binding and H3K4me1 patterns in other cell types, these studies suggest that simple combinations of lineage-determining transcription factors can specify the genomic sites ultimately responsible for both cell identity and cell type-specific responses to diverse signaling inputs.
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影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
E2A蛋白促进淋巴酸化的多能祖细胞的发展。
影响因子：
32.4
作者：
Dias, Sheila;Mansson, Robert;Gurbuxani, Sandeep;Sigvardsson, Mikael;Kee, Barbara L.
通讯作者：
Kee, Barbara L.
影响因子：
21.3
作者：
Feng, Bo;Jiang, Jianming;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui
影响因子：
64.5
作者：
Adolfsson, J;Månsson, R;Jacobsen, SEW
通讯作者：
Jacobsen, SEW
影响因子：
32.4
作者：
Ikawa, T;Kawamoto, H;Murre, C
通讯作者：
Murre, C