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Publication : ZIC3 Controls the Transition from Naive to Primed Pluripotency.

First Author  Yang SH Year  2019
Journal  Cell Rep Volume  27
Issue  11 Pages  3215-3227.e6
PubMed ID  31189106 Mgi Jnum  J:288406
Mgi Id  MGI:6432061 Doi  10.1016/j.celrep.2019.05.026
Citation  Yang SH, et al. (2019) ZIC3 Controls the Transition from Naive to Primed Pluripotency. Cell Rep 27(11):3215-3227.e6
abstractText  Embryonic stem cells (ESCs) must transition through a series of intermediate cell states before becoming terminally differentiated. Here, we investigated the early events in this transition by determining the changes in the open chromatin landscape as naive mouse ESCs transition to epiblast-like cells (EpiLCs). Motif enrichment analysis of the newly opening regions coupled with expression analysis identified ZIC3 as a potential regulator of this cell fate transition. Chromatin binding and genome-wide transcriptional profiling following Zic3 depletion confirmed ZIC3 as an important regulatory transcription factor, and among its targets are genes encoding a number of transcription factors. Among these is GRHL2, which acts through enhancer switching to maintain the expression of a subset of genes from the ESC state. Our data therefore place ZIC3 upstream of a set of pro-differentiation transcriptional regulators and provide an important advance in our understanding of the regulatory factors governing the early steps in ESC differentiation.
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