Fei F, Xia K, Li Z, Zhou B, Zhu S, Chen H, Zhang J, Chen Z, Xiao H, Han JD#, Chen YG# Genome-wide Mapping of Smad Target Genes Reveals the Role of BMP Signaling in Embryonic Stem Cell Fate Determination. GENOME RESEARCH, 20:36-44, 2010

Abstract Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades. How external signaling pathways connect to core self-renewal transcriptional circuits is largely unknown. To probe this, we chose BMP signaling, which is previously recognized as a master control for both self-renewal and lineage commitment of murine ES cells. Here, we mapped target gene promoter occupancy of SMAD1/5 and SMAD4 on a genome-wide scale and found that they associate with a large group of developmental regulators that are enriched for H3K27 trimethylation and H3K4 trimethylation bivalent marks and are repressed in the self-renewing state, whereas they are rapidly induced upon differentiation. Smad knockdow......