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Human SETMAR is a DNA sequence-specific histone-methylase with a broad effect on the transcriptome

Tellier, Michael; Chalmers, Ronald

Authors

Michael Tellier michael.tellier@path.ox.ac.uk

RONALD CHALMERS RONALD.CHALMERS@NOTTINGHAM.AC.UK
Professor of Biochemistry and Cell Biology



Abstract

Transposons impart dynamism to the genomes they inhabit and their movements frequently rewire the control of nearby genes. Occasionally, their proteins are domesticated when they evolve a new function. SETMAR is a protein methylase with a sequence-specific DNA binding domain. It began to evolve about 50 million years ago when an Hsmar1 transposon integrated downstream of a SET-domain methylase gene. Here we show that the DNA-binding domain of the transposase targets the enzyme to transposon-end remnants and that this is capable of regulating gene expression, dependent on the methylase activity. When SETMAR was modestly overexpressed in human cells, almost 1500 genes changed expression by more than 2-fold (65% up- and 35% down-regulated). These genes were enriched for the KEGG Pathways in Cancer and include several transcription factors important for development and differentiation. Expression of a similar level of a methylase-deficient SETMAR changed the expression of many fewer genes, 77% of which were down-regulated with no significant enrichment of KEGG Pathways. Our data is consistent with a model in which SETMAR is part of an anthropoid primate-specific regulatory network centered on the subset of genes containing a transposon end.

Citation

Tellier, M., & Chalmers, R. (2019). Human SETMAR is a DNA sequence-specific histone-methylase with a broad effect on the transcriptome. Nucleic Acids Research, 47(1), 122–133. https://doi.org/10.1093/nar/gky937

Journal Article Type Article
Acceptance Date Oct 12, 2018
Online Publication Date Oct 17, 2018
Publication Date Jan 10, 2019
Deposit Date Nov 1, 2018
Publicly Available Date Nov 1, 2018
Journal Nucleic Acids Research
Print ISSN 0305-1048
Electronic ISSN 1362-4962
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 47
Issue 1
Pages 122–133
DOI https://doi.org/10.1093/nar/gky937
Keywords Genetics
Public URL https://nottingham-repository.worktribe.com/output/1217389
Publisher URL https://academic.oup.com/nar/article/47/1/122/5133659

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