Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2.
Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2.
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DOI：
10.1016/j.devcel.2010.10.006
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发表时间：
2010-11-16
影响因子：
11.8
通讯作者：
Shivdasani, Ramesh A.
中科院分区：
文献类型：
--
作者：
Verzi, Michael P.;Shin, Hyunjin;He, H. Hansen;Sulahian, Rita;Meyer, Clifford A.;Montgomery, Robert K.;Fleet, James C.;Brown, Myles;Liu, X. Shirley;Shivdasani, Ramesh A.
细胞分化需要重塑组织特异性基因位点和关键转录调控因子的活性，这些转录调控因子被认为是对细胞程序的主导控制。使用表观基因组学方法，我们的特点是增强子元件在分化肠上皮细胞特异性修饰，并发现富集的转录因子结合基序对应的CDX2，一个关键的调节肠道。定向研究揭示了CDX2在基因组中占据的惊人不稳定性，从仅在增殖细胞中占据的数百个位点重新分布到分化细胞中的数千个新位点。敲除小鼠证实了不同的Cdx2分裂和成熟的成年肠细胞的要求，包括与成熟相关的活性增强子配置的责任。动态CDX2占用对应于条件特异性基因表达，重要的是，与其他组织限制性转录因子如GATA 6和HNF 4A的差异共占用。这些结果揭示了动态的，上下文特定的功能和机制的一个突出的转录调节细胞谱系内。
Cell differentiation requires remodeling of tissue-specific gene loci and activities of key transcriptional regulators, which are recognized for their dominant control over cellular programs. Using epigenomic methods, we characterized enhancer elements specifically modified in differentiating intestinal epithelial cells and found enrichment of transcription factor-binding motifs corresponding to CDX2, a critical regulator of the intestine. Directed investigation revealed surprising lability in CDX2 occupancy of the genome, with redistribution from hundreds of sites occupied only in proliferating cells to thousands of new sites in differentiated cells. Knockout mice confirmed distinct Cdx2 requirements in dividing and mature adult intestinal cells, including responsibility for the active enhancer configuration associated with maturity. Dynamic CDX2 occupancy corresponds with condition-specific gene expression and, importantly, to differential co-occupancy with other tissue-restricted transcription factors such as GATA6 and HNF4A. These results reveal dynamic, context-specific functions and mechanisms of a prominent transcriptional regulator within a cell lineage.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
29.4
作者：
Hinoi, T;Lucas, PC;Fearon, ER
通讯作者：
Fearon, ER
影响因子：
30.8
作者：
He, Housheng Hansen;Meyer, Clifford A.;Shin, Hyunjin;Bailey, Shannon T.;Wei, Gang;Wang, Qianben;Zhang, Yong;Xu, Kexin;Ni, Min;Lupien, Mathieu;Mieczkowski, Piotr;Lieb, Jason D.;Zhao, Keji;Brown, Myles;Liu, X. Shirley
通讯作者：
Liu, X. Shirley
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
影响因子：
4.6
作者：
D'Angelo, Anna;Bluteau, Olivier;Pontoglio, Marco
通讯作者：
Pontoglio, Marco