The TIF1?-HP1 system maintains transcriptional integrity of hematopoietic stem cells.

ABSTRACT: TIF1? 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 TIF1? 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 (HP1?, ? and ?) proteins, which form a complex with TIF1?, were significantly reduced in the absence of TIF1? and depletion of HP1 recapitulated a part of the phenotypes of Tif1b-deficient HSCs. These results demonstrate that the TIF1?-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.

SUBMITTER: Miyagi S 

PROVIDER: S-EPMC3923190 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature