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Publication : The TIF1β-HP1 system maintains transcriptional integrity of hematopoietic stem cells.

First Author  Miyagi S Year  2014
Journal  Stem Cell Reports Volume  2
Issue  2 Pages  145-52
PubMed ID  24527388 Mgi Jnum  J:318230
Mgi Id  MGI:6858846 Doi  10.1016/j.stemcr.2013.12.008
Citation  Miyagi S, et al. (2014) The TIF1beta-HP1 system maintains transcriptional integrity of hematopoietic stem cells. Stem Cell Reports 2(2):145-52
abstractText  TIF1beta 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 TIF1beta 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 (HP1alpha, beta and gamma) proteins, which form a complex with TIF1beta, were significantly reduced in the absence of TIF1beta and depletion of HP1 recapitulated a part of the phenotypes of Tif1b-deficient HSCs. These results demonstrate that the TIF1beta-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.
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