Human SETMAR is a DNA sequence-specific histone-methylase with a broad effect on the transcriptome.
Animals
DNA Transposable Elements
/ genetics
DNA-Binding Proteins
/ chemistry
Gene Expression Regulation, Neoplastic
/ genetics
Gene Regulatory Networks
/ genetics
Histone Methyltransferases
/ chemistry
Histone-Lysine N-Methyltransferase
/ genetics
Histones
/ genetics
Humans
Methylation
Neoplasms
/ genetics
Primates
/ genetics
Signal Transduction
/ genetics
Transcription Factors
/ chemistry
Transcriptome
/ genetics
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
10 01 2019
10 01 2019
Historique:
received:
30
07
2018
accepted:
12
10
2018
pubmed:
18
10
2018
medline:
23
8
2019
entrez:
18
10
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30329085
pii: 5133659
doi: 10.1093/nar/gky937
pmc: PMC6326780
doi:
Substances chimiques
DNA Transposable Elements
0
DNA-Binding Proteins
0
Histones
0
Transcription Factors
0
Histone Methyltransferases
EC 2.1.1.-
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
SETMAR protein, human
EC 2.1.1.43
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
122-133Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/J014508/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/J014508/1
Pays : United Kingdom
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