RRC ID |
50044
|
著者 |
Matsuda K, Mikami T, Oki S, Iida H, Andrabi M, Boss JM, Yamaguchi K, Shigenobu S, Kondoh H.
|
タイトル |
ChIP-seq analysis of genomic binding regions of five major transcription factors highlights a central role for ZIC2 in the mouse epiblast stem cell gene regulatory network.
|
ジャーナル |
Development
|
Abstract |
To obtain insight into the transcription factor (TF)-dependent regulation of epiblast stem cells (EpiSCs), we performed ChIP-seq analysis of the genomic binding regions of five major TFs. Analysis of in vivo biotinylated ZIC2, OTX2, SOX2, POU5F1 and POU3F1 binding in EpiSCs identified several new features. (1) Megabase-scale genomic domains rich in ZIC2 peaks and genes alternate with those rich in POU3F1 but sparse in genes, reflecting the clustering of regulatory regions that act at short and long-range, which involve binding of ZIC2 and POU3F1, respectively. (2) The enhancers bound by ZIC2 and OTX2 prominently regulate TF genes in EpiSCs. (3) The binding sites for SOX2 and POU5F1 in mouse embryonic stem cells (ESCs) and EpiSCs are divergent, reflecting the shift in the major acting TFs from SOX2/POU5F1 in ESCs to OTX2/ZIC2 in EpiSCs. (4) This shift in the major acting TFs appears to be primed by binding of ZIC2 in ESCs at relevant genomic positions that later function as enhancers following the disengagement of SOX2/POU5F1 from major regulatory functions and subsequent binding by OTX2. These new insights into EpiSC gene regulatory networks gained from this study are highly relevant to early stage embryogenesis.
|
巻・号 |
144(11)
|
ページ |
1948-1958
|
公開日 |
2017-6-1
|
DOI |
10.1242/dev.143479
|
PII |
dev.143479
|
PMID |
28455373
|
PMC |
PMC5482983
|
MeSH |
Animals
Binding Sites / genetics
Biotinylation
Chromatin Immunoprecipitation*
Gene Expression Regulation, Developmental*
Gene Regulatory Networks*
Genome
Germ Layers / cytology*
Germ Layers / metabolism
Humans
Mice
Mouse Embryonic Stem Cells / cytology
Mouse Embryonic Stem Cells / metabolism*
Octamer Transcription Factor-3 / metabolism
Otx Transcription Factors / metabolism
Protein Binding
SOXB1 Transcription Factors / metabolism
Sequence Analysis, RNA*
Transcription Factors / genetics
Transcription Factors / metabolism*
|
IF |
5.611
|
引用数 |
15
|
リソース情報 |
遺伝子材料 |
pCAGGS-BLRP-BirA (RDB15774) |