Combinatorial assembly of developmental stage-specific enhancers controls gene expression programs during human erythropoiesis.

Combinatorial assembly of developmental stage-specific enhancers controls gene expression programs during human erythropoiesis.
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DOI:
10.1016/j.devcel.2012.09.003
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发表时间:
2012-10-16
期刊:
影响因子:
11.8
通讯作者:
Orkin, Stuart H.
Orkin, Stuart H.
中科院分区:
生物学1区
文献类型:
--
作者:
Xu, Jian;Shao, Zhen;Glass, Kimberly;Bauer, Daniel E.;Pinello, Luca;Van Handel, Ben;Hou, Serena;Stamatoyannopoulos, John A.;Mikkola, Hanna K. A.;Yuan, Guo-Cheng;Orkin, Stuart H.

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Gene-distal enhancers are critical for tissue-specific gene expression, but their genomic determinants within a specific lineage at different stages of development are unknown. Here we profile chromatin state maps, transcription factor occupancy, and gene expression profiles during human erythroid development at fetal and adult stages. Comparative analyses of human erythropoiesis identify developmental stage-specific enhancers as primary determinants of stage-specific gene expression programs. We find that erythroid master regulators GATA1 and TAL1 act cooperatively within active enhancers but confer little predictive value for stage specificity. Instead, a set of stage-specific co-regulators collaborates with master regulators and contributes to differential gene expression. We further identify and validate IRF2, IRF6, and MYB as effectors of an adult-stage expression program. Thus, the combinatorial assembly of lineage-specific master regulators and transcriptional co-regulators within developmental stage-specific enhancers determines gene expression programs and temporal regulation of transcriptional networks in a mammalian genome.
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发表时间: 2009-11-25
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影响因子: 8
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