Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells
Transcription factors (TFs) and their specific interactions with targets are crucial for specifying gene expression programs. To gain insights into the transcriptional regulatory networks in embryonic stem (ES) cells, we use chromatin immunoprecipitation coupled with ultra high throughput DNA sequencing (ChIP seq) to map the locations of 13 sequence specific TFs (Nanog, Oct4, STAT3, Smad1, Sox2, Zfx, c Myc, n Myc, Klf4, Esrrb, Tcfcp2l1, E2f1, and CTCF) and 2 transcription regulators (p300 and Suz12) These factors are known to play different roles in ES cell biology as components of the LIF and BMP signaling pathways, self renewal regulators, and key reprogramming factors. Our study provides insights into the integration of the signaling pathways into the ES cell specific transcription circuitries. Intriguingly, we find specific genomic regions extensively targeted by different TFs. Collectively, the comprehensive mapping of TF binding sites identifies important features of the transcriptional regulatory networks that define ES cell identity.
Cell