| Overlapping functions of Hdac1 and Hdac2 in cell cycle regulation and haematopoiesis. | |
| | |
MedLine Citation:
|
PMID: 20571512 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Histone deacetylases (HDACs) counterbalance acetylation of lysine residues, a protein modification involved in numerous biological processes. Here, Hdac1 and Hdac2 conditional knock-out alleles were used to study the function of class I Hdac1 and Hdac2 in cell cycle progression and haematopoietic differentiation. Combined deletion of Hdac1 and Hdac2, or inactivation of their deacetylase activity in primary or oncogenic-transformed fibroblasts, results in a senescence-like G(1) cell cycle arrest, accompanied by up-regulation of the cyclin-dependent kinase inhibitor p21(Cip). Notably, concomitant genetic inactivation of p53 or p21(Cip) indicates that Hdac1 and Hdac2 regulate p53-p21(Cip)-independent pathways critical for maintaining cell cycle progression. In vivo, we show that Hdac1 and Hdac2 are not essential for liver homeostasis. In contrast, total levels of Hdac1 and Hdac2 in the haematopoietic system are critical for erythrocyte-megakaryocyte differentiation. Dual inactivation of Hdac1 and Hdac2 results in apoptosis of megakaryocytes and thrombocytopenia. Together, these data indicate that Hdac1 and Hdac2 have overlapping functions in cell cycle regulation and haematopoiesis. In addition, this work provides insights into mechanism-based toxicities observed in patients treated with HDAC inhibitors. |
| | |
Authors:
|
Roel H Wilting; Eva Yanover; Marinus R Heideman; Heinz Jacobs; James Horner; Jaco van der Torre; Ronald A DePinho; Jan-Hermen Dannenberg |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-22 |
Journal Detail:
|
Title: The EMBO journal Volume: 29 ISSN: 1460-2075 ISO Abbreviation: EMBO J. Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-08-04 Completed Date: 2010-08-26 Revised Date: 2011-08-25 |
Medline Journal Info:
|
Nlm Unique ID: 8208664 Medline TA: EMBO J Country: England |
Other Details:
|
Languages: eng Pagination: 2586-97 Citation Subset: IM |
Affiliation:
|
Division of Molecular Genetics, Plesmanlaan 121, Amsterdam, The Netherlands. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Anemia
/
enzymology Animals Apoptosis Biocatalysis Cell Cycle* Cells, Cultured Cyclin-Dependent Kinase Inhibitor p21 / deficiency, metabolism Hematopoiesis* Histone Deacetylase 1 / deficiency, metabolism* Histone Deacetylase 2 / deficiency, metabolism* Humans Mice Mice, Inbred C57BL Mice, Knockout Thrombocytopenia / enzymology, pathology Tumor Suppressor Protein p53 / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Cdkn1a protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Tumor Suppressor Protein p53; EC 3.5.1.98/Hdac1 protein, mouse; EC 3.5.1.98/Hdac2 protein, mouse; EC 3.5.1.98/Histone Deacetylase 1; EC 3.5.1.98/Histone Deacetylase 2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Elg1, an alternative subunit of the RFC clamp loader, preferentially interacts with SUMOylated PCNA.
Next Document: Independent fusions and recent origins of sex chromosomes in the evolution and diversification of gl...