Nucleosome deposition and DNA methylation at coding region boundaries.

Background: Nucleosome deposition downstream of transcription initiation and DNA methylation in the gene body suggest that control of transcription elongation is a key aspect of epigenetic regulation.

Results: Here we report a genome-wide observation of distinct peaks of nucleosomes and methylation at both ends of a protein coding unit. Elongating polymerases tend to pause near both coding ends immediately upstream of the epigenetic peaks, causing a significant reduction in elongation efficiency. Conserved features in underlying protein coding sequences seem to dictate their evolutionary conservation across multiple species. The nucleosomal and methylation marks are commonly associated with high sequence-encoded DNA-bending propensity but differentially with CpG density. As the gene grows longer, the epigenetic codes seem to be shifted from variable inner sequences toward boundary regions, rendering the peaks more prominent in higher organisms.

Conclusions: Recent studies suggest that epigenetic inhibition of transcription elongation facilitates the inclusion of constitutive exons during RNA splicing. The epigenetic marks we identified here seem to secure the first and last coding exons from exon skipping as they are indispensable for accurate translation.