BAF60 A, B, and Cs of muscle determination and renewal - PubMed (original) (raw)

Review

BAF60 A, B, and Cs of muscle determination and renewal

Pier Lorenzo Puri et al. Genes Dev. 2012.

Abstract

Developmental biologists have defined many of the diffusible and transcription factors that control muscle differentiation, yet we still have only rudimentary knowledge of the mechanisms that dictate whether a myogenic progenitor cell forms muscle versus alternate lineages, including those that can be pathological in a state of disease or degeneration. Clues about the molecular basis for lineage determination in muscle progenitors are only now emerging from studies of chromatin modifications that avail myogenic genes for transcription, together with analysis of the composition and activities of the chromatin-modifying complexes themselves. Here we review recent progress on muscle determination and explore a unifying theme that environmental cues from the stem or progenitor niche control the selection of specific subunit variants of the switch/sucrose nonfermentable (SWI/SNF) chromatin-modifying complex, creating a combinatorial code that dictates whether cells adopt myogenic versus nonmyogenic cell fates. A key component of the code appears to be the mutually exclusive usage of the a, b, and c variants of the 60-kD structural subunit BAF60 (BRG1/BRM-associated factor 60), of which BAF60c is essential to activate both skeletal and cardiac muscle programs. Since chromatin remodeling governs myogenic fate, the combinatorial assembly of the SWI/SNF complex might be targeted to develop drugs aimed at the therapeutic reduction of compensatory fibrosis and fatty deposition in chronic muscular disorders.

PubMed Disclaimer

Figures

Figure 1.

Figure 1.

Combinatorial logic of SWI/SNF assembly and lineage diversification. The chromatin remodeling catalytic core of SWI/SNF consists of one of the two ATPase subunits, BRG1 or BRM, with BAF47, BAF155, and BAF170. Emerging evidence suggests that selective activation of lineage-specific constellations of genes might be achieved through the combinatorial assembly of variants of the other BAF structural subunits, which are bridged to sites in chromatin by their interactions with specific transcription factors; for example, MyoD and GATA4 for skeletal and cardiac myogenesis, respectively. Hundreds of combinations are possible, yielding a potentially rich lineage determining “code” (discussed in detail in Wu 2012) that might drive the selection of myogenic versus nonmyogenic cell fates.

Figure 2.

Figure 2.

A model for environmental control over stem cell fate. Regulation of SWI/SNF subunit composition might connect environmental cues to the differentiation response of a stem cell. Signals that increase the expression and usage of BAF subunits that favor activation of myogenic genes would be regenerative. In contrast, maladaptive signals in chronic myopathy could be hostile for regeneration by biasing the SWI/SNF combinatorial “code” against myogenesis and in favor of pathological fibrosis or adipocyte deposition.

Similar articles

Cited by

References

    1. Asakura A, Komaki M, Rudnicki M 2001. Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation. Differentiation 68: 245–253 - PubMed
    1. Asp P, Blum R, Vethantham V, Parisi F, Micsinai M, Cheng J, Bowman C, Kluger Y, Dynlacht BD 2011. Genome-wide remodeling of the epigenetic landscape during myogenic differentiation. Proc Natl Acad Sci 108: E149–E158 doi: 10.1073/pnas.1102223108 - PMC - PubMed
    1. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, et al. 2003. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114: 763–776 - PubMed
    1. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, et al. 2009. Evidence for cardiomyocyte renewal in humans. Science 324: 98–102 - PMC - PubMed
    1. Berkes CA, Bergstrom DA, Penn BH, Seaver KJ, Knoepfler PS, Tapscott SJ 2004. Pbx marks genes for activation by MyoD indicating a role for a homeodomain protein in establishing myogenic potential. Mol Cell 14: 465–477 - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources