TY - JOUR
T1 - The TIF1β-HP1 system maintains transcriptional integrity of hematopoietic stem cells
AU - Miyagi, Satoru
AU - Koide, Shuhei
AU - Saraya, Atsunori
AU - Wendt, George R.
AU - Oshima, Motohiko
AU - Konuma, Takaaki
AU - Yamazaki, Satoshi
AU - Mochizuki-Kashio, Makiko
AU - Nakajima-Takagi, Yaeko
AU - Wang, Changshan
AU - Chiba, Tetsuhiro
AU - Kitabayashi, Issay
AU - Nakauchi, Hiromitsu
AU - Iwama, Atsushi
PY - 2014/2/11
Y1 - 2014/2/11
N2 - TIF1β is a transcriptional corepressor that recruits repressive chromatin modifiers to target genes. Its biological function and physiological targets in somatic stem cells remain largely unknown. Here, we show that TIF1β is essential for the maintenance of hematopoietic stem cells (HSCs). Deletion of Tif1b in mice induced active cycling and apoptosis of HSCs and promoted egression of HSCs from the bone marrow, leading to rapid depletion of HSCs. Strikingly, Tif1b-deficient HSCs showed a strong trend of ectopic expression of nonhematopoietic genes. Levels of heterochromatin protein 1 (HP1α, β and γ) proteins, which form a complex with TIF1β, were significantly reduced in the absence of TIF1β and depletion of HP1 recapitulated a part of the phenotypes of Tif1b-deficient HSCs. These results demonstrate that the TIF1β-HP1 system functions as a critical repressive machinery that targets genes not normally activated in the hematopoietic compartment, thereby maintaining the transcriptional signature specific to HSCs.
AB - TIF1β is a transcriptional corepressor that recruits repressive chromatin modifiers to target genes. Its biological function and physiological targets in somatic stem cells remain largely unknown. Here, we show that TIF1β is essential for the maintenance of hematopoietic stem cells (HSCs). Deletion of Tif1b in mice induced active cycling and apoptosis of HSCs and promoted egression of HSCs from the bone marrow, leading to rapid depletion of HSCs. Strikingly, Tif1b-deficient HSCs showed a strong trend of ectopic expression of nonhematopoietic genes. Levels of heterochromatin protein 1 (HP1α, β and γ) proteins, which form a complex with TIF1β, were significantly reduced in the absence of TIF1β and depletion of HP1 recapitulated a part of the phenotypes of Tif1b-deficient HSCs. These results demonstrate that the TIF1β-HP1 system functions as a critical repressive machinery that targets genes not normally activated in the hematopoietic compartment, thereby maintaining the transcriptional signature specific to HSCs.
UR - http://www.scopus.com/inward/record.url?scp=84893722267&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893722267&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2013.12.008
DO - 10.1016/j.stemcr.2013.12.008
M3 - Article
C2 - 24527388
AN - SCOPUS:84893722267
SN - 2213-6711
VL - 2
SP - 145
EP - 152
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 2
ER -