The TIF1β-HP1 system maintains transcriptional integrity of hematopoietic stem cells.
The TIF1β-HP1 system maintains transcriptional integrity of hematopoietic stem cells.
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TIF1β-HP1系统保持造血干细胞的转录完整性。
DOI：
10.1016/j.stemcr.2013.12.008
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发表时间：
2014-02-11
影响因子：
5.9
通讯作者：
Iwama, Atsushi
中科院分区：
文献类型：
--
作者：
Miyagi, Satoru;Koide, Shuhei;Saraya, Atsunori;Wendt, George R.;Oshima, Motohiko;Konuma, Takaaki;Yamazaki, Satoshi;Mochizuki-Kashio, Makiko;Nakajima-Takagi, Yaeko;Wang, Changshan;Chiba, Tetsuhiro;Kitabayashi, Issay;Nakauchi, Hiromitsu;Iwama, Atsushi
Tif1β是一种转录辅阻遏子，它招募抑制染色质修饰物来靶向基因。它在体细胞中的生物学功能和生理靶点仍然很大程度上是未知的。在这里，我们表明TIF1β对于维持造血干细胞(HSCs)是必不可少的。Tif1b基因缺失可诱导HSCs的活跃周期和凋亡，并促进HSCs从骨髓中排出，导致HSCs的快速耗竭。值得注意的是，Tif1b缺陷的HSCs表现出强烈的异位表达非造血基因的趋势。异染色质蛋白1(Hp1α，β和γ)蛋白与Tif1β形成复合体，在缺乏Tif1β的情况下显著降低，Hp1的缺失概括了Tif1b缺陷的HSCs的部分表型。这些结果表明，TIF1β-HP1系统作为一个关键的抑制机制，针对通常不在造血室中激活的基因，从而维持HSCs特有的转录特征。在小鼠中Tif1b的缺失会导致HSCs的快速耗尽Tif1β的丢失导致Hp1蛋白的减少Tif1β-Hp1系统抑制HSCs中的非造血基因Tif1β-Hp1系统帮助维持HSCs的转录完整性岩间弥生及他的同事证明Tif1β是一种转录抑制因子，它招募抑制性染色质修饰物到靶基因，对于造血干细胞的维持是必不可少的。在与Hp1蛋白的协作中，Tif1β作为一种关键的抑制机制，针对通常不在造血室中激活的基因，从而维持HSCs特有的转录特征。
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. Deletion of Tif1b in mice causes rapid depletion of HSCs Loss of TIF1β leads to reduction in HP1 proteins in HSCs The TIF1β-HP1 system represses nonhematopoietic genes in HSCs The TIF1β-HP1 system helps maintain the transcriptional integrity of HSCs Iwama and colleagues show that TIF1β, a transcriptional corepressor that recruits repressive chromatin modifiers to target genes, is essential for the maintenance of hematopoietic stem cells. In collaboration with HP1 proteins, TIF1β functions as a critical repressive machinery that targets genes not normally activated in the hematopoietic compartment, thereby maintaining the transcriptional signature specific to HSCs.
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影响因子：
10.5
作者：
Yoshida, Toshimi;Hazan, Idit;Georgopoulos, Katia
通讯作者：
Georgopoulos, Katia
DOI：
10.1242/dev.087585
发表时间：
2013-02-01
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Rowe HM;Friedli M;Offner S;Verp S;Mesnard D;Marquis J;Aktas T;Trono D
通讯作者：
Trono D
影响因子：
10.5
作者：
Schultz, DC;Friedman, JR;Rauscher, FJ
通讯作者：
Rauscher, FJ
影响因子：
11.4
作者：
Nielsen, AL;Ortiz, JA;Losson, R
通讯作者：
Losson, R
影响因子：
64.8
作者：
Rowe, Helen M.;Jakobsson, Johan;Trono, Didier
通讯作者：
Trono, Didier