Histone Acetyltransferase Cofactor Trrap Is Essential for Maintaining the Hematopoietic Stem/Progenitor Cell Pool

Autor: Andreas Trumpp, Carla Sawan, Rabih Murr, Zhao-Qi Wang, Zdenko Herceg, Gabriela M. Oser, Joanna I. Loizou, Vivek Shukla
Rok vydání: 2009
Předmět:
Coenzymes/immunology/metabolism
Immunology
Coenzymes
Apoptosis
Biology
Mice
Bone Marrow
medicine
Animals
Immunology and Allergy
Progenitor cell
Tissue homeostasis
Adaptor Proteins
Signal Transducing
Histone Acetyltransferases
Mice
Knockout
Genetics
Bone Marrow/immunology/metabolism
Histone Acetyltransferases/immunology/metabolism
Nuclear Proteins
Histone acetyltransferase
Hematopoietic Stem Cells
Tumor Suppressor Protein p53/genetics/immunology/metabolism
Mice
Mutant Strains
Cell biology
Chromatin
Adaptor Proteins
Signal Transducing/genetics/immunology/metabolism
Nuclear Proteins/genetics/immunology/metabolism
Haematopoiesis
Histone
medicine.anatomical_structure
biology.protein
Hematopoietic Stem Cells/immunology/metabolism
Bone marrow
Tumor Suppressor Protein p53
Stem cell
Apoptosis/immunology
Zdroj: Journal of Immunology, Vol. 183, No 10 (2009) pp. 6422-31
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.0901969
Popis: The pool of hematopoietic stem/progenitor cells, which provide life-long reconstitution of all hematopoietic lineages, is tightly controlled and regulated by self-renewal and apoptosis. Histone modifiers and chromatin states are believed to govern establishment, maintenance, and propagation of distinct patterns of gene expression in stem cells, however the underlying mechanism remains poorly understood. In this study, we identified a role for the histone acetytransferase cofactor Trrap in the maintenance of hematopietic stem/progenitor cells. Conditional deletion of the Trrap gene in mice resulted in ablation of bone marrow and increased lethality. This was due to the depletion of early hematopoietic progenitors, including hematopoietic stem cells, via a cell-autonomous mechanism. Analysis of purified bone marrow progenitors revealed that these defects are associated with induction of p53-independent apoptosis and deregulation of Myc transcription factors. Together, this study has identified a critical role for Trrap in the mechanism that maintains hematopoietic stem cells and hematopoietic system, and underscores the importance of Trrap and histone modifications in tissue homeostasis.
Databáze: OpenAIRE
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