The TIF1β-HP1 System Maintains Transcriptional Integrity of Hematopoietic Stem Cells

TIF1 beta 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 beta is essential for the maintenance of hematopoietic stem cells (HSCs). Deletion of TIF1 beta 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, TIF1 beta-deficient HSCs showed a strong trend of ectopic expression of nonhematopoietic genes. Levels of heterochromatin protein 1 (HP1 alpha, beta and gamma) proteins, which form a complex with TIF1 beta, were significantly reduced in the absence of TIF1 beta and depletion of HP1 recapitulated a part of the phenotypes of TIF1 beta-deficient HSCs. These results demonstrate that the TIF1 beta-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.