title: The TIF1β-HP1 system maintains transcriptional integrity of hematopoietic stem cells.
abstract: 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.
authors: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan ; JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors: Satoru
authors: S
authors: Miyagi
authors: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan ; JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors: Shuhei
authors: S
authors: Koide
authors: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan ; JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors: Atsunori
authors: A
authors: Saraya
authors: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan ; ITO Foundation for International Education Exchange, Shinjuku 160-0023, Japan.
authors: George R
authors: GR
authors: Wendt
authors: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan ; JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors: Motohiko
authors: M
authors: Oshima
authors: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors: Takaaki
authors: T
authors: Konuma
authors: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors: Satoshi
authors: S
authors: Yamazaki
authors: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan ; JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors: Makiko
authors: M
authors: Mochizuki-Kashio
authors: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan ; JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors: Yaeko
authors: Y
authors: Nakajima-Takagi
authors: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan ; JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors: Changshan
authors: C
authors: Wang
authors: Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors: Tetsuhiro
authors: T
authors: Chiba
authors: Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors: Issay
authors: I
authors: Kitabayashi
authors: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors: Hiromitsu
authors: H
authors: Nakauchi
authors: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan ; JST, CREST, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors: Atsushi
authors: A
authors: Iwama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002478:Cells, Cultured; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D005333:Fetus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D018390:Gene Targeting; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D011485:Protein Binding; D034622:RNA Interference; D014158:Transcription, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D000090266:Chromobox Protein Homolog 5; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator