Sequence and epigenetic determinants in the regulation of the Math6 gene by Neurogenin3

Publication year: 2011
Source: Differentiation, In Press, Corrected Proof, Available online 14 June 2011

Gemma, Pujadas , Francesc, Felipe , Miriam, Ejarque , Lidia, Sanchez , Sara, Cervantes , …

The bHLH factor Neurogenin3 initiates the differentiation program that leads to formation of pancreatic endocrine cells. Math6 is a closely related bHLH factor transiently activated downstream of Neurogenin3 in endocrine progenitors. Here we characterize the Math6 promoter and locate the Neurogenin3 binding site, thus confirming that Math6 is a genuine Neurogenin3 target. We also show that Math6 activation rates are largely controlled by epigenetic mechanisms involving the balance between activating H3K4 and repressive H3K27 methylation marks. High Math6 expression in the embryonic pancreas associates with an H3K4me3-only state, whereas low Math6 expression in differentiated endocrine cells correlates with chromatin dually…