Evolution of lysine acetylation in the RNA polymerase II C-terminal domain

BMC Evolutionary Biology

John A Capra²  Melanie Ott³  Benoit G Bruneau³  Daniel He³  Sebastian Schröder³  Katherine S Pollard¹  Corinne N Simonti⁴ 

[1] Department of Epidemiology & Biostatistics and Institute for Human Genetics, University of California, San Francisco, San Francisco 94158, CA, USA;Departments of Biological Sciences and Biomedical Informatics, Vanderbilt University, Nashville 37232, TN, USA;Gladstone Institutes, University of California, San Francisco, San Francisco 94158, CA, USA;Center for Human Genetics Research, Vanderbilt University, Nashville 37232, TN, USA

关键词: Phylogenetics;    Metazoa;    Posttranslational modification;    RNA pol II acetylation;    Heptad repeats;    RNA pol II C-terminal domain;   

Others  :  1158292
DOI  :  10.1186/s12862-015-0327-z

 received in 2014-11-24, accepted in 2015-02-24,  发布年份 2015

【 摘 要 】

Background

RPB1, the largest subunit of RNA polymerase II, contains a highly modifiable C-terminal domain (CTD) that consists of variations of a consensus heptad repeat sequence (Y₁S₂P₃T₄S₅P₆S₇). The consensus CTD repeat motif and tandem organization represent the ancestral state of eukaryotic RPB1, but across eukaryotes CTDs show considerable diversity in repeat organization and sequence content. These differences may reflect lineage-specific CTD functions mediated by protein interactions. Mammalian CTDs contain eight non-consensus repeats with a lysine in the seventh position (K₇). Posttranslational acetylation of these sites was recently shown to be required for proper polymerase pausing and regulation of two growth factor-regulated genes.

Results

To investigate the origins and function of RPB1 CTD acetylation (acRPB1), we computationally reconstructed the evolution of the CTD repeat sequence across eukaryotes and analyzed the evolution and function of genes dysregulated when acRPB1 is disrupted. Modeling the evolutionary dynamics of CTD repeat count and sequence content across diverse eukaryotes revealed an expansion of the CTD in the ancestors of Metazoa. The new CTD repeats introduced the potential for acRPB1 due to the appearance of distal repeats with lysine at position seven. This was followed by a further increase in the number of lysine-containing repeats in developmentally complex clades like Deuterostomia. Mouse genes enriched for acRPB1 occupancy at their promoters and genes with significant expression changes when acRPB1 is disrupted are enriched for several functions, such as growth factor response, gene regulation, cellular adhesion, and vascular development. Genes occupied and regulated by acRPB1 show significant enrichment for evolutionary origins in the early history of eukaryotes through early vertebrates.

Conclusions

Our combined functional and evolutionary analyses show that RPB1 CTD acetylation was possible in the early history of animals, and that the K₇ content of the CTD expanded in specific developmentally complex metazoan lineages. The functional analysis of genes regulated by acRPB1 highlight functions involved in the origin of and diversification of complex Metazoa. This suggests that acRPB1 may have played a role in the success of animals.

【 授权许可】

   
2015 Simonti et al.; licensee BioMed Central.

【 图 表 】

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