Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 6
p38 Mitogen-Activated Protein Kinase Pathway Regulates the Transcription of Skeletal
Muscle Late Genes .
Eyal Bengal1, Bennett H Penn2 and Stephen J Tapscott2.
1Department of Biochemistry, Rappaport Institute for Research in the Medical
Sciences,Faculty of Medicine. Technion-Israel Institute of Technology. P.O. Box 9649.
Haifa 31096, Israel. email: bengal@tx.technion.ac.il and 2 Division of Human Biology,
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024 USA.
The p38 mitogen-activated protein kinase (MAPK) pathway is induced during the
differentiation of proliferating myoblasts to multinucleated myotubes and is absolutely
essential for this process to occur in cell cultures.
Previous work showed that the p38 pathway augmented the activity of transcription factors
from the MEF2 and MyoD families. Here, we present data suggesting that only a small
subgroup of muscle-specific genes is regulated by p38 MAPK. A DNA microarray analysis
performed on muscle cells expressing an activated MKK6 protein revealed that the p38
MAPK pathway was involved in the expression of several muscle-structural genes.
Expression of these late-activated genes was shifted to the early stages of differentiation by
precocious activation of p38 and expression of Mef2D.
To understand how p38 MAPK regulates the transcription of these genes, we performed a
chromatin immunoprecipitation (ChIP) analysis. We show that p38 activity facilitates MyoD
and Mef2 binding at a subset of late-activated promoters, and the binding of Mef2D recruits
Pol II.
This demonstrates that a MyoD-generated feed-forward regulatory circuit, wherein factors
induced by MyoD feed-forward to regulate MyoD activity at subsequent target genes, acts to
temporally pattern the relative timing of gene expression during skeletal myogenesis.
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