Temporal regulation of chromatin during myoblast differentiation

Abstract

The commitment to and execution of differentiation programs involves a significant change in gene expression in the precursor cell to facilitate development of the mature cell type. In addition to being regulated by lineage-determining and auxiliary transcription factors that drive these changes, the structural status of the chromatin has a considerable impact on the transcriptional competence of differentiation-specific genes, which is clearly demonstrated by the large number of cofactors and the extraordinary complex mechanisms by which these genes become activated. The terminal differentiation of myoblasts to myotubes and mature skeletal muscle is an excellent system to illustrate these points. The MyoD family of closely related, lineage-determining transcription factors directs, largely through targeting to chromatin, a cascade of cooperating transcription factors and enzymes that incorporate or remove variant histones, post-translationally modify histones, and alter nucleosome structure and positioning via energy released by ATP hydrolysis. The coordinated action of these transcription factors and enzymes prevents expression of differentiation-specific genes in myoblasts and facilitates the transition of these genes from transcriptionally repressed to activated during the differentiation process. Regulation is achieved in both a temporal as well as spatial manner, as at least some of these factors and enzymes affect local chromatin structure at myogenic gene regulatory sequences as well as higher-order genome organization. Here we discuss the transition of genes that promote myoblast differentiation from the silenced to the activated state with an emphasis on the changes that occur to individual histones and the chromatin structure present at these loci.

CBP and P300 regulate distinct gene networks required for human primary myoblast differentiation and muscle integrity

“…While CBP and/or P300 were shown in cell-based assays to act as co-activators for several transcription factors critically involved in myogenesis, such as MyoD, Myogenin or Mef2C 9 – 12 , their respective function in this process remains poorly characterised. Vertebrate myogenesis requires the cooperation of the myogenic regulatory factors (MRFs) MyoD, Myf5, Mrf4 and Myogenin 13 , and the members of the Myocyte-enhancer factors 2 (Mef2) family, with chromatin remodelling or modifying enzymes (for reviews, 14 – 17 . Myoblast differentiation is a sequential process that starts by the withdrawal from the cell cycle, followed by the expression of factors involved in the muscle specific transcriptional program.…”

miR-206 knockout shows it is critical for myogenesis and directly regulates newly identified target mRNAs

“…Together our data support the conclusion that Adam19, Bgn, Cbx5, Smarce1, and Spg20 are novel miR-206 targets These newly identified mRNA targets have interesting connections to skeletal muscle differentiation. Cbx5 and Smarce1 are both chromatin regulators and terminal differentiation of skeletal muscle involves chromatin reorganization (36). Cbx5 (Hp1a) can interact with and inhibit the activity of MyoD, a necessary transcription factor in myogenic commitment (37).…”

SWI/SNF coordinates transcriptional activation through Rpd3-mediated histone hypoacetylation during quiescence entry

“…These results are reminiscent of the role of SWI/SNF in responding to signaling cascades to facilitate differentiation. For instance, the Baf60 component of the mammalian SWI/SNF complex binds to myogenic gene promoters prior to the onset of differentiation signaling for chromatin to be remodeled by the catalytic subunits after signaling has been initiated (Forcales, 2012;Harada et al, 2017;Simone et al, 2004).…”