H3K9 methylation and RNA interference regulate

H3K9 methylation and RNA interference regulate

标题：H3K9 methylation and RNA interference regulate
nucleolar organization and repeated DNA stability
来源：Nature Cell Biology , 10 December 2006;
作者：Jamy C.Peng1,2 and Gary H. Karpen1,2,3
文摘：Investigations aimed at identifying regulators of nuclear
architecture in Drosophila demonstrated that cells lacking
H3K9 methylation and RNA interference (RNAi) pathway
components displayed disorganized nucleoli, ribosomal DNA
(rDNA) and satellite DNAs. The levels of H3K9 dimethylation
(H3K9me2) in chromatin associated with repeated DNAs
decreased dramatically in Su(var)3-9 and dcr-2 (dicer-2)
mutant tissues compared with wild type. We also observed
a substantial increase in extrachromosomal circular (ecc)
repeated DNAs in mutant tissues. The disorganized nucleolus
phenotype depends on the presence of Ligase 4 and ecc DNA
formation is not induced by removal of cohesin. We conclude
that the structural integrity and organization of repeated DNAs
and nucleoli are regulated by the H3K9 methylation and RNAi
pathways, and other regulators of heterochromatin-mediated
silencing. In addition, repeated DNA stability involves
suppression of non-homologous end joining (NHEJ) or other
recombination pathways. These results suggest a mechanism
for how local chromatin structure can regulate genome
stability, and the organization of chromosomal elements and
nuclear organelles.