Regulation of HDAC11 gene expression in early myogenic differentiation.

Histone acetylation and deacetylation affect the patterns of gene expression in cellular differentiation, playing pivotal roles in tissue development and maintenance. For example, the intrinsic histone acetyltransferase activity of transcriptional coactivator p300 is especially required for the expression of myogenic regulatory factors including Myf5 and MyoD, and consequently for skeletal myogenesis. On the other hand, histone deacetylases (HDACs) remove the acetyl group from histones, which is critical for gene repression in stem cell fate transition. Through integrative omic analyses, we found that while some HDACs were differentially expressed at the early stage of skeletal myoblast differentiation, Hdac11 gene expression was significantly enhanced by nuclear receptor signaling. In addition, p300 and MyoD control Hdac11 expression in milieu of normal and signal-enhanced myoblast differentiation. Thus, HDAC11 may be essential to differential gene expression at the onset of myoblast differentiation.

Chromatin state distribution of residue-specific histone acetylation in early myoblast differentiation.

Dynamic changes in epigenetic landscape reflect a critical command of lineage-specific gene expression. In an effort to discern the epigenetic regulatory networks of myogenic differentiation, we have used systematic and integrative approaches to explore multi-omics datasets on global myogenic gene expression, histone acetylation and acetyltransferase occupancy in view of distinct chromatin states. In this brief report, we discuss experimental design and provide a comprehensive assessment regarding data quality control, filtering and processing. We also define a gene-level overlap between RNA-seq and ChIP-seq datasets through integrative analyses to offer strategies for future use of the data. Furthermore, our analyses generate a blueprint on chromatin state distribution of residue-specific histone acetylation and concomitant association with histone acetyltransferase p300 in committed skeletal myoblasts and differential histone acetylation signatures at the onset of myoblast differentiation. These datasets can be further utilized to delineate the function of muscle-specific regulatory elements governed by other muscle myogenic regulators or signaling molecules.