Epigenomic annotation of enhancers predicts transcriptional regulators of human neural crest.
Epigenomic annotation of enhancers predicts transcriptional regulators of human neural crest.
复制标题
DOI：
10.1016/j.stem.2012.07.006
复制
发表时间：
2012-11-02
期刊：
影响因子：
23.9
通讯作者：
Wysocka, Joanna
中科院分区：
文献类型：
--
作者：
Rada-Iglesias, Alvaro;Bajpai, Ruchi;Prescott, Sara;Brugmann, Samantha A.;Swigut, Tomek;Wysocka, Joanna
神经脊细胞(NCC)是一种瞬时的胚胎细胞群，具有异常的迁移能力和发育可塑性。为了注释和表征人类NCC所利用的顺式调控元件，我们将hESC分化模型与全基因组组蛋白修饰、辅激活子和转录因子(Tf)占据情况相结合。序列分析预测了主要的转录因子结合在表观组学注释的HNCC增强子上，包括主NC调节因子TFAP2A以及核受体NR2F1和NR2F2。虽然许多TF结合事件发生在增强子之外，但在从鸡胚分离的NCC中，与增强子染色质特征一致的位置显示出显著更高的序列限制、核小体耗竭、与基因表达的相关性和功能保守性。TFAP2A和NR2F1/F2的同时共存与允许的增强子染色质状态有关，其特征是高水平的p300和H3K27ac。我们的结果首次提供了对人类NC染色质景观的全球洞察，并为颅面发育和疾病的研究提供了丰富的资源。
Neural Crest Cells (NCC) are a transient, embryonic cell population characterized by unusual migratory ability and developmental plasticity. To annotate and characterize cis-regulatory elements utilized by the human NCC we coupled a hESC differentiation model with genome-wide profiling of histone modifications, coactivator and transcription factor (TF) occupancy. Sequence analysis predicted major TFs binding at epigenomically annotated hNCC enhancers, including master NC regulator, TFAP2A, and nuclear receptors NR2F1 and NR2F2. Although many TF binding events occur outside enhancers, sites coinciding with enhancer chromatin signatures show significantly higher sequence constraint, nucleosomal depletion, correlation with gene expression and functional conservation in NCC isolated from chicken embryos. Simultaneous co-occupancy of TFAP2A and NR2F1/F2 is associated with permissive enhancer chromatin states, characterized by high levels of p300 and H3K27ac. Our results provide first global insights into human NC chromatin landscapes and a rich resource for studies of craniofacial development and disease.
登录
查看更多内容
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：
4.8
作者：
Kaltschmidt, Barbara;Kaltschmidt, Christian;Widera, Darius
通讯作者：
Widera, Darius
影响因子：
4.6
作者：
Aybar, MJ;Nieto, MA;Mayor, R
通讯作者：
Mayor, R
影响因子：
30.8
作者：
Birnbaum, Stefanie;Ludwig, Kerstin U.;Mangold, Elisabeth
通讯作者：
Mangold, Elisabeth
影响因子：
20.1
作者：
Ivey KN;Sutcliffe D;Richardson J;Clyman RI;Garcia JA;Srivastava D
通讯作者：
Srivastava D