"In this new paper in Cell, the team at the GIS continues their remarkable progress in defining the precise DNA sequences to which an important group of 13 transcriptional factors bind in mouse embryonic stem cells," said Alan Colman, Ph.D., Executive Director of Singapore's Stem Cell Consortium. "This particular group of factors is responsible for maintaining the self renewal and pluripotency of the embryonic stem cells. The team shows that many of the factors which bind to the same gene regions ('hotspots') and their work provide a working model of the transcriptional networks at play within the cells, and how these intracellular networks are linked to events that can be influenced by external stimuli."
The researchers performed genome-wide mapping of the in vivo binding sites for 13 sequence-specific transcription factors in ES cells. These transcription factors play different roles in self-renewal, pluripotency, reprogramming and chromatin insulation. This study uncovers two major modes of binding that give rise to transcription factor co- localization hotspots. The Nanog/Oct4/Sox2 centric hotspots are commonly co-bound by Smad1 and STAT3 and they represent points of integration for the intrinsic and external signaling pathways. The combinatorial wiring of transcription factors is important in deciphering the code behind gene expression program in ES cells.
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