Epigenetic regulation of gene expression is instructed by promoter sequence and refined by developmental progression [expression]

A large body of literature suggests that local features of chromatin are crucial in determining functional properties of underlying DNA. The extent to which DNA sequence plays an active role in the establishment and maintenance of patterns of histone and DNA modification at promoters in cells and tissues in an adult animal remains poorly understood. Likewise, whether passage through development is required for refinement of transcriptional states and chromatin marks characteristic of fully differentiated adult cells remains unclear. Here we undertook analysis of gene expression along with the genomic distribution of DNA methylation and a set of histone marks in primary tissues derived from different primordial germ layers in adult mice. We find that promoter CpG content correlated strongly with specific repressive mechanisms. Likewise, RNA polymerase II occupancy and active histone marks were omnipresent on CpG rich promoters regardless of transcriptional output and of cell type. However, these same chromatin features cleanly demarcate transcriptional activity on promoters with low CpG content. While these observations imply an instructive role for DNA sequence in establishment and maintenance of epigenetic states, experimental evidence presented here also suggests an additional role for development in refining these features at individual promoters. Gene expression in B cells and liver was measured using Agilent Whole Mouse Genome 4x44 multiplex format oligo arrays.