Format

Send to

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

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

Author information

1
Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany.
2
Genome Function Group, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
3
Graduate Program in Areas of Basic and Applied Biology, University of Porto, Porto, Portugal.
4
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.

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

PMID:
26687004
PMCID:
PMC4758952
DOI:
10.7554/eLife.11215
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center