Methylation of RNA polymerase II non-consensus Lysine residues marks early transcription in mammalian cells

Elife. 2015 Dec 19;4:e11215. doi: 10.7554/eLife.11215.

Abstract

Dynamic post-translational modification of RNA polymerase II (RNAPII) coordinates the co-transcriptional recruitment of enzymatic complexes that regulate chromatin states and processing of nascent RNA. Extensive phosphorylation of serine residues at the largest RNAPII subunit occurs at its structurally-disordered C-terminal domain (CTD), which is composed of multiple heptapeptide repeats with consensus sequence Y1-S2-P3-T4-S5-P6-S7. Serine-5 and Serine-7 phosphorylation mark transcription initiation, whereas Serine-2 phosphorylation coincides with productive elongation. In vertebrates, the CTD has eight non-canonical substitutions of Serine-7 into Lysine-7, which can be acetylated (K7ac). Here, we describe mono- and di-methylation of CTD Lysine-7 residues (K7me1 and K7me2). K7me1 and K7me2 are observed during the earliest transcription stages and precede or accompany Serine-5 and Serine-7 phosphorylation. In contrast, K7ac is associated with RNAPII elongation, Serine-2 phosphorylation and mRNA expression. We identify an unexpected balance between RNAPII K7 methylation and acetylation at gene promoters, which fine-tunes gene expression levels.

Keywords: C-terminal domain; RNA polymerase II; chromosomes; computational biology; genes; methylation; mouse; non-histone protein lysine methylation; post-transcriptional modification; systems biology; transcription cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Consensus
  • Gene Expression Regulation*
  • Lysine / metabolism*
  • Methylation
  • Mice
  • NIH 3T3 Cells
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • RNA Polymerase II / metabolism*
  • Serine / metabolism
  • Transcription, Genetic*

Substances

  • Serine
  • RNA Polymerase II
  • Lysine