Genetic and Epigenetic Determinants of Neurogenesis and Myogenesis

Abstract

SUMMARY The regulatory networks of differentiation programs have been partly characterized; however, the molecular mechanisms of lineage-specific gene regulation by highly similar transcription factors remain largely unknown. Here we compare the genome-wide binding and transcription profiles of NEUROD2-mediated neurogenesis with MYOD-mediated myogenesis. We demonstrate that NEUROD2 and MYOD bind a shared CAGCTG E-box motif and E-box motifs specific for each factor: CAGGTG for MYOD and CAGATG for NEUROD2. Binding at factor-specific motifs is associated with gene transcription, whereas binding at shared sites is associated with regional epigenetic modifications but not as strongly associated with gene transcription. Binding is largely constrained to E-boxes pre-set in an accessible chromatin context that determines the set of target genes activated in each cell type. These findings demonstrate that the differentiation program is genetically determined by E-box sequence whereas cell lineage epigenetically determines the availability of E-boxes for each differentiation program.

Mesogenin 1 is a master regulator of paraxial presomitic mesoderm differentiation

“…The only known tissue and developmental stage that Msgn1 is expressed is in the mesenchymal cells of the PSM, making Msgn1 a remarkably stage-and tissuespecific transcription factor. Our studies demonstrate that Msgn1 regulates the EMT and PSM differentiation programs by binding to a unique E-box sequence that is distinct from the binding sites for Twist1 (Eckert et al, 2011), MyoD and NeuroD1 (Fong et al, 2012). Other non-bHLH EMT transcription factors, such as the Zn-finger homeodomain-containing factors Zeb1 and Zeb2, also function by binding to E-boxes and closely related Z-boxes (Burk et al, 2008).…”

Loci-specific histone acetylation profiles associated with transcriptional coactivator p300 during early myoblast differentiation

“…Remarkably, studies of histone acetylation in the context of terminal differentiation have observed a near-complete loss of H3K9ac in contrast to a high level of H3K18ac on genes activated in myotubes as compared to proliferating myoblasts [4,16]. Furthermore, the association of MyoD to distinct E-box motifs generally corresponds to enhancer assembly, marked by H3K27ac, and muscle-specific gene expression during myotube formation [16,17]. As a result, MyoD binding is an index of myogenic enhancers [1], leading to the recruitment of histone acetyltransferases (HATs), which deposit the acetyl moiety required for enhancer activation [16].…”

Epigenetics and developmental programming of welfare and production traits in farm animals

“…Expression of myogenin is a key step in myogenic differentiation, and changes in DNA methylation patterns at this locus have been identified as differentiation proceeds and this gene is induced (Fuso et al 2010;Palacios et al 2010). DNA binding of MyoD and induction of muscle-determining genes is also regulated by epigenetic changes to binding sites in the promoters of its target genes (Fong et al 2012). Dynamic changes in DNA modification regulate myogenic commitment and differentiation (Tsumagari et al 2013), and global changes in DNA methylation patterns have been mapped in fast-and slow-growing strains of chicken, evidence for a direct epigenetic effect on muscle growth (Hu et al 2013b).…”