Genome-wide binding of the basic helix-loop-helix myogenic inhibitor musculin has substantial overlap with MyoD: implications for buffering activity.

Autor: MacQuarrie KL; Human Biology Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N C3-168, Seattle WA 98109, USA.; Molecular and Cellular Biology Program, University of Washington, Seattle WA 98105, USA., Yao Z; Human Biology Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N C3-168, Seattle WA 98109, USA., Fong AP; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA.; Department of Pediatrics, University of Washington School of Medicine, Seattle WA 98105, USA., Tapscott SJ; Human Biology Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N C3-168, Seattle WA 98109, USA.; Department of Neurology, University of Washington, Seattle WA 98105, USA.
Jazyk: angličtina
Zdroj: Skeletal muscle [Skelet Muscle] 2013 Nov 01; Vol. 3 (1), pp. 26. Date of Electronic Publication: 2013 Nov 01.
DOI: 10.1186/2044-5040-3-26
Abstrakt: Background: Musculin (MSC) is a basic helix-loop-helix transcription factor that inhibits myogenesis during normal development and contributes to the differentiation defect in rhabdomyosarcoma. As one of many transcription factors that impede myogenesis, its binding on a genome-wide scale relative to the widespread binding of the myogenic factor MyoD is unknown.
Methods: Chromatin immunoprecipitation coupled to high-throughput sequencing was performed for endogenous MSC in rhabdomyosarcoma cells and its binding was compared to that of MyoD in the same type of cells.
Results: MSC binds throughout the genome, in a pattern very similar to MyoD. Its binding overlaps strongly with regions enriched for acetylated histone H4, as well as regions that score high for DNase hypersensitivity in human myoblasts. In contrast to MyoD, MSC has a more relaxed binding sequence preference in the nucleotides that flank the core E-box motif.
Conclusions: The myogenic inhibitor MSC binds throughout the genome of rhabdomyosarcoma cells, in a pattern highly similar to that of MyoD, suggesting a broad role in buffering the activity of MyoD in development and rhabdomyosarcomas.
Databáze: MEDLINE
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