PR-SET7 and SUV4-20H regulate H4 lysine-20 methylation at imprinting control regions in the mouse.
Imprinted genes are important in development and their allelic expression is mediated by imprinting control regions (ICRs). On their DNA-methylated allele, ICRs are marked by trimethylation at H3 Lys 9 (H3K9me3) and H4 Lys 20 (H4K20me3), similar to pericentric heterochromatin. Here, we investigate which histone methyltransferases control this methylation of histone at ICRs. We found that inactivation of SUV4-20H leads to the loss of H4K20me3 and increased levels of its substrate, H4K20me1. H4K20me1 is controlled by PR-SET7 and is detected on both parental alleles. The disruption of SUV4-20H or PR-SET7 does not affect methylation of DNA at ICRs but influences precipitation of H3K9me3, which is suggestive of a trans-histone change. Unlike at pericentric heterochromatin, however, H3K9me3 at ICRs does not depend on SUV39H. Our data show not only new similarities but also differences between ICRs and heterochromatin, both of which show constitutive maintenance of methylation of DNA in somatic cells.
Pannetier
Maëlle
M
Institute of Molecular Genetics, CNRS and University of Montpellier, 1919 Route de Mende, 34293 Montpellier, France.
Julien
Eric
E
Schotta
Gunnar
G
Tardat
Mathieu
M
Sardet
Claude
C
Jenuwein
Thomas
T
Feil
Robert
R
D000818:Animals; D019175:DNA Methylation; D018392:Genomic Imprinting / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase / Q000502:physiology*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008780:Methyltransferases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013379:Substrate Specificity / Q000235:genetics
D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D008239:Lysine; D008780:Methyltransferases; D012097:Repressor Proteins; C498700:Suv39h1 protein, mouse; C529566:KMT5a protein, mouse