Contrasting roles for MyoD in organizing myogenic promoter structures during embryonic skeletal muscle development
Department of Cell and Developmental Biology
Cell and Developmental Biology | Cell Biology | Developmental Biology
BACKGROUND: Among the complexities of skeletal muscle differentiation is a temporal distinction in the onset of expression of different lineage-specific genes. The lineage-determining factor MyoD is bound to myogenic genes at the onset of differentiation whether gene activation is immediate or delayed. How temporal regulation of differentiation-specific genes is established remains unclear.
RESULTS: Using embryonic tissue, we addressed the molecular differences in the organization of the myogenin and muscle creatine kinase (MCK) gene promoters by examining regulatory factor binding as a function of both time and spatial organization during somitogenesis. At the myogenin promoter, binding of the homeodomain factor Pbx1 coincided with H3 hyperacetylation and was followed by binding of co-activators that modulate chromatin structure. MyoD and myogenin binding occurred subsequently, demonstrating that Pbx1 facilitates chromatin remodeling and modification before myogenic regulatory factor binding. At the same time, the MCK promoter was bound by HDAC2 and MyoD, and activating histone marks were largely absent. The association of HDAC2 and MyoD was confirmed by co-immunoprecipitation, proximity ligation assay (PLA), and sequential ChIP.
CONCLUSIONS: MyoD differentially promotes activated and repressed chromatin structures at myogenic genes early after the onset of skeletal muscle differentiation in the developing mouse embryo.
Pbx, gene expression, gene regulation, histone deacetylase, myogenesis, somite
DOI of Published Version
Dev Dyn. 2015 Jan;244(1):43-55. doi: 10.1002/dvdy.24217. Epub 2014 Nov 3. Link to article on publisher's site.
Developmental dynamics : an official publication of the American Association of Anatomists
Cho OH, Mallappa C, Hernandez JM, Rivera-Perez JA, Imbalzano AN. (2015). Contrasting roles for MyoD in organizing myogenic promoter structures during embryonic skeletal muscle development. Cell and Developmental Biology Publications. https://doi.org/10.1002/dvdy.24217. Retrieved from https://escholarship.umassmed.edu/cellbiology_pp/142