E-MTAB-1583 - Transcription profiling by array of human human embryonic stem cells after knockdown of ERK2 and ELK1 to investigate the transcriptional regulatory network of ERK/MAPK signaling
Released on 31 May 2013, last updated on 3 June 2014
The ERK/MAPK signal transduction cascade is one of the key pathways regulating proliferation and differentiation in development and disease. In human embryonic stem cells (hESCs), ERK signaling is required for their self-renewing property. Here we studied the convergence of the ERK signaling cascade at the DNA by mapping genome-wide kinase-chromatin interactions for ERK2 in hESCs. We observe that ERK2 targets genes coding for small RNAs, histones, and genes involved in cellular metabolism and cell cycle. We find that the transcription factor ELK1 is essential in hESCs and that ERK2 co-occupies promoters bound by ELK1. Strikingly, promoters bound by ELK1 without ERK2 are occupied by Polycomb group proteins that repress genes involved in lineage commitment. In summary, we propose a model where extracellular signaling-stimulated proliferation and intrinsic repression of differentiation is integrated to maintain the identity of hESCs.
transcription profiling by array, cellular modification, co-expression, in vitro
Genome-wide Kinase-Chromatin Interactions Reveal the Regulatory Network of ERK Signaling in Human Embryonic Stem Cells. Jonathan Goke, Yun-Shen Chan, Junli Yan, Martin Vingron, Huck-Hui Ng. Mol Cell 50:1-12 (2013)