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Demethylated HSATII DNA and HSATII RNA Foci Sequester PRC1 and MeCP2 into
Cancer-Specific Nuclear Bodies
#MMPMID28329686
Hall LL
; Byron M
; Carone DM
; Whitfield TW
; Pouliot GP
; Fischer A
; Jones P
; Lawrence JB
Cell Rep
2017[Mar]; 18
(12
): 2943-2956
PMID28329686
show ga
This study reveals that high-copy satellite II (HSATII) sequences in the human
genome can bind and impact distribution of chromatin regulatory proteins and that
this goes awry in cancer. In many cancers, master regulatory proteins form two
types of cancer-specific nuclear bodies, caused by locus-specific deregulation of
HSATII. DNA demethylation at the 1q12 mega-satellite, common in cancer, causes
PRC1 aggregation into prominent Cancer-Associated Polycomb (CAP) bodies. These
loci remain silent, whereas HSATII loci with reduced PRC1 become derepressed,
reflecting imbalanced distribution of UbH2A on these and other PcG-regulated
loci. Large nuclear foci of HSATII RNA form and sequester copious MeCP2 into
Cancer-Associated Satellite Transcript (CAST) bodies. Hence, HSATII DNA and RNA
have an exceptional capacity to act as molecular sponges and sequester chromatin
regulatory proteins into abnormal nuclear bodies in cancer. The
compartmentalization of regulatory proteins within nuclear structure, triggered
by demethylation of "junk" repeats, raises the possibility that this contributes
to further compromise of the epigenome and neoplastic progression.
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