TitleGenetic and epigenetic determinants of neurogenesis and myogenesis.
Publication TypeJournal Article
Year of Publication2012
AuthorsFong AP, Yao Z, Zhong J W, Cao Y, Ruzzo WL, Gentleman RC, Tapscott SJ
JournalDevelopmental Cell
Date or Month Published2012 Apr 17
AbstractThe 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 is not as strongly associated with gene transcription. Binding is largely constrained to E boxes preset 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.
Alternate JournalDev. Cell
Citation Key7816
PubMed ID22445365