Dataset Information


Genome-Wide Sox17 Binding Sites in Mouse Extraembryonic Endoderm and Embryonic Stem Cells

ABSTRACT: We investigated whether Sox17 directly or indirectly regulates extraembryonic endoderm gene expression by identifying Sox17 DNA-binding sites using chromatin-immunoprecipitation coupled with whole-genome promoter tiling array analysis (ChIP-Chip). We used the Sox17 and FLAG antibody to ask whether Sox17 was binding directly to the regulatory regions of genes in homogeneous extraembryonic endoderm (XEN) cell lines and in Sox17-inducible mouse embryonic stem (ES) cells. In XEN cells, Sox17 binding sites were located within the promoters or the introns of 2206 (3%) genes. We performed an ontology analysis for the genes with Sox17 binding sites and found that a significant number had adhesion functions in basement membrane establishment and maintenance. In addition to these ECM genes, Sox17 was also bound to promoter regions of a variety of other genes implicated in extraembryonic endoderm development including key transcription factors. Ontology analysis of all the Sox17 ChIP-chip binding targets identified in Sox17-induced ES cells, demonstrated a significant enrichment near genes involved in the cell cycle as well as genes involved in signaling pathways that function in embryonic stem cell maintenance. Sox17 was also observed to directly bind to the regulatory regions of many genes in pathways known to be functionally important for ES cell pluripotency and self-renewal. These studies suggest that one of Sox17’s functions in the differentiation of ICM and ES cells is to bind the regulatory regions of many genes that encode basement membrane components, thus leading to their activation. In addition to directly activating genes required for primitive endoderm differentiation, Sox17 may also function to activate and reinforce the transcriptional network governing differentiation. Overall design: Extraembryonic endoderm (XEN) mouse cell lines ChIPed with Sox17 vs. XEN cell Input; Sox17-inducible mouse ES cells (induced with doxycycline for 48hrs) ChIPed with Sox17 or FLAG vs. Input

INSTRUMENT(S): [Mm_PromPR] Affymetrix Mouse Promoter 1.0R Array

SUBMITTER: Kathy Niakan 

PROVIDER: GSE19026 | GEO | 2010-03-31



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Sox17 promotes differentiation in mouse embryonic stem cells by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal.

Niakan Kathy K KK   Ji Hongkai H   Maehr René R   Vokes Steven A SA   Rodolfa Kit T KT   Sherwood Richard I RI   Yamaki Mariko M   Dimos John T JT   Chen Alice E AE   Melton Douglas A DA   McMahon Andrew P AP   Eggan Kevin K  

Genes & development 20100201 3

In embryonic stem (ES) cells, a well-characterized transcriptional network promotes pluripotency and represses gene expression required for differentiation. In comparison, the transcriptional networks that promote differentiation of ES cells and the blastocyst inner cell mass are poorly understood. Here, we show that Sox17 is a transcriptional regulator of differentiation in these pluripotent cells. ES cells deficient in Sox17 fail to differentiate into extraembryonic cell types and maintain exp  ...[more]

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