Reorganization of enhancer patterns in transition from naive to primed pluripotency.

Reorganization of enhancer patterns in transition from naive to primed pluripotency.
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DOI:
10.1016/j.stem.2014.04.003
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发表时间:
2014-06-05
期刊:
影响因子:
23.9
通讯作者:
Wysocka, Joanna
Wysocka, Joanna
中科院分区:
医学1区
文献类型:
--
作者:
Buecker, Christa;Srinivasan, Rajini;Wu, Zhixiang;Calo, Eliezer;Acampora, Dario;Faial, Tiago;Simeone, Antonio;Tan, Minjia;Swigut, Tomasz;Wysocka, Joanna

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Naïve and primed pluripotency is characterized by distinct signaling requirements, transcriptomes and developmental properties, but both cellular states share key transcriptional regulators, Oct4, Sox2 and Nanog. Here we demonstrate that transition between these two pluripotent states is associated with widespread Oct4 relocalization, mirrored by global rearrangement of enhancer chromatin landscapes. Our genomic and biochemical analyses identified candidate mediators of primed state-specific Oct4 binding, including Otx2 and Zic2/3. Even when differentiation cues are blocked, premature Otx2 overexpression is sufficient to exit the naïve state, induce transcription of a substantial subset of primed pluripotency-associated genes and redirect Oct4 to previously inaccessible enhancer sites. However, ability of Otx2 to engage new enhancer regions is determined by its levels, cis-encoded properties of the sites and signaling environment. Our results illuminate regulatory mechanisms underlying pluripotency and suggest that capacity of transcription factors such as Otx2 and Oct4 to pioneer new enhancer sites is highly context-dependent.
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发表时间: 2011-04-01
期刊: Bioinformatics (Oxford, England)
影响因子: --
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通讯作者: Noble WS
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