Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability.
Histone H3 lysine 9 methylation has been proposed to provide a major "switch" for the functional organization of chromosomal subdomains. Here, we show that the murine Suv39h histone methyltransferases (HMTases) govern H3-K9 methylation at pericentric heterochromatin and induce a specialized histone methylation pattern that differs from the broad H3-K9 methylation present at other chromosomal regions. Suv39h-deficient mice display severely impaired viability and chromosomal instabilities that are associated with an increased tumor risk and perturbed chromosome interactions during male meiosis. These in vivo data assign a crucial role for pericentric H3-K9 methylation in protecting genome stability, and define the Suv39h HMTases as important epigenetic regulators for mammalian development.
Peters
A H
AH
Research Institute of Molecular Pathology (IMP), Vienna Biocenter, Dr. Bohrgasse 7, A-1030, Vienna, Austria.
O'Carroll
D
D
Scherthan
H
H
Mechtler
K
K
Sauer
S
S
Schöfer
C
C
Weipoltshammer
K
K
Pagani
M
M
Lachner
M
M
Kohlmaier
A
A
Opravil
S
S
Doyle
M
M
Sibilia
M
M
Jenuwein
T
T
D000782:Aneuploidy; D000818:Animals; D020090:Chromosome Segregation / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology; D018390:Gene Targeting / Q000379:methods; D016678:Genome; D005854:Germ Cells; D006570:Heterochromatin / Q000502:physiology*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D007006:Hypogonadism; D016393:Lymphoma, B-Cell; D008297:Male; D008322:Mammals; D008540:Meiosis; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D011496:Protein Methyltransferases; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012729:Sex Chromosome Aberrations; D013090:Spermatocytes; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology
D006570:Heterochromatin; D006657:Histones; D012097:Repressor Proteins; C498700:Suv39h1 protein, mouse; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase