Human SETMAR is a DNA sequence-specific histone-methylase with a broad effect on the transcriptome.
Nucleic Acids Res
; 47(1): 122-133, 2019 01 10.
Article
in En
| MEDLINE
| ID: mdl-30329085
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Histone-Lysine N-Methyltransferase
/
DNA-Binding Proteins
/
Transcriptome
/
Histone Methyltransferases
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Nucleic Acids Res
Year:
2019
Document type:
Article
Affiliation country:
United kingdom