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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Genes+Dev
2014 ; 28
(24
): 2712-25
Nephropedia Template TP
gab.com Text
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English Wikipedia
HIRA orchestrates a dynamic chromatin landscape in senescence and is required for
suppression of neoplasia
#MMPMID25512559
Rai TS
; Cole JJ
; Nelson DM
; Dikovskaya D
; Faller WJ
; Vizioli MG
; Hewitt RN
; Anannya O
; McBryan T
; Manoharan I
; van Tuyn J
; Morrice N
; Pchelintsev NA
; Ivanov A
; Brock C
; Drotar ME
; Nixon C
; Clark W
; Sansom OJ
; Anderson KI
; King A
; Blyth K
; Adams PD
Genes Dev
2014[Dec]; 28
(24
): 2712-25
PMID25512559
show ga
Cellular senescence is a stable proliferation arrest that suppresses
tumorigenesis. Cellular senescence and associated tumor suppression depend on
control of chromatin. Histone chaperone HIRA deposits variant histone H3.3 and
histone H4 into chromatin in a DNA replication-independent manner. Appropriately
for a DNA replication-independent chaperone, HIRA is involved in control of
chromatin in nonproliferating senescent cells, although its role is poorly
defined. Here, we show that nonproliferating senescent cells express and
incorporate histone H3.3 and other canonical core histones into a dynamic
chromatin landscape. Expression of canonical histones is linked to alternative
mRNA splicing to eliminate signals that confer mRNA instability in
nonproliferating cells. Deposition of newly synthesized histones H3.3 and H4 into
chromatin of senescent cells depends on HIRA. HIRA and newly deposited H3.3
colocalize at promoters of expressed genes, partially redistributing between
proliferating and senescent cells to parallel changes in expression. In senescent
cells, but not proliferating cells, promoters of active genes are exceptionally
enriched in H4K16ac, and HIRA is required for retention of H4K16ac. HIRA is also
required for retention of H4K16ac in vivo and suppression of oncogene-induced
neoplasia. These results show that HIRA controls a specialized, dynamic
H4K16ac-decorated chromatin landscape in senescent cells and enforces tumor
suppression.