Regulation ofMyf5Early Enhancer by Histone Acetyltransferase p300 during Stem Cell Differentiation.
Skeletal myogenesis is an intricate process coordinated temporally by multiple myogenic regulatory factors (MRF) including Myf5, which is the first MRF expressed and marks the commitment of skeletal muscle lineage. The expression of Myf5 gene during early embryogenesis is controlled by a set of enhancer elements, and requires the histone acetyltransferase (HAT) activity of transcriptional coactivator p300. However, it is unclear as to how different regulatory signals converge at enhancer elements to regulate early Myf5 gene expression, and if p300 is directly involved. We show here that p300 associates with theMyf5early enhancer at the early stage of stem cell differentiation, and its HAT activity is important for the recruitment of β-catenin to this early enhancer. In addition, histone H3-K27 acetylation, but not H3-K9/14, is intimately connected to the p300 HAT activity. Thus, p300 is directly involved in the regulation of theMyf5early enhancer, and is important for specific histone acetylation and transcription factor recruitment. This connection of p300 HAT activity with H3-K27 acetylation and β-catenin signalling during myogenic differentiationin vitrooffers a molecular insight into the enhancer-elements participation observed in embryonic development. In addition, pluripotent stem cell differentiation is a valuable system to dissect the signal-dependent regulation of specific enhancer element during cell fate determinations.
Cellular and Molecular, Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON Canada.
Tanja
T
Francetic
Cellular and Molecular, Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON Canada.
Melanie
M
Le May
Cellular and Molecular, Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON Canada.
Munerah
M
Hamed
Departments of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON Canada.
Hymn
H
Mach
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD USA.
David
D
Meyers
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD USA.
Philip A
PA
Cole
Departments of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON Canada.
Jihong
J
Chen
Departments of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON Canada ; Cellular and Molecular, Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON Canada.
Qiao
Q
Li
Acetyltransferase; Gene regulation; Histone acetylation; Regulatory elements; Stem cell differentiation; Transcription factor