The histone acetyl transferase activity of monocytic leukemia zinc finger is critical for the proliferation of hematopoietic precursors.

2.50
Hdl Handle:
http://hdl.handle.net/10541/74014
Title:
The histone acetyl transferase activity of monocytic leukemia zinc finger is critical for the proliferation of hematopoietic precursors.
Authors:
Perez-Campo, Flor-Maria; Borrow, Julian; Kouskoff, Valerie; Lacaud, Georges
Abstract:
The monocytic leukemia zinc finger (MOZ) gene encodes a large multidomain protein that contains, besides other domains, 2 coactivation domains for the transcription factor Runx1/acute myeloid leukemia 1 and a histone acetyl transferase (HAT) catalytic domain. Recent studies have demonstrated the critical requirement for the complete MOZ protein in hematopoietic stem cell development and maintenance. However, the specific function of the HAT activity of MOZ remains unknown, as it has been shown that MOZ HAT activity is not required either for its role as Runx1 coactivator or for the leukemic transformation induced by MOZ transcriptional intermediary factor 2 (TIF2). To assess the specific requirement for this HAT activity during hematopoietic development, we have generated embryonic stem cells and mouse lines carrying a point mutation that renders the protein catalytically inactive. We report in this study that mice exclusively lacking the HAT activity of MOZ exhibit significant defects in the number of hematopoietic stem cells and hematopoietic committed precursors as well as a defect in B-cell development. Furthermore, we demonstrate that the failure to maintain a normal number of hematopoietic precursors is caused by the inability of HAT(-/-) cells to expand. These results indicate a specific role of MOZ-driven acetylation in controlling a desirable balance between proliferation and differentiation during hematopoiesis.
Affiliation:
Paterson Institute for Cancer Research, University of Manchester, USA.
Citation:
The histone acetyl transferase activity of monocytic leukemia zinc finger is critical for the proliferation of hematopoietic precursors. 2009, 113 (20):4866-74 Blood
Journal:
Blood
Issue Date:
14-May-2009
URI:
http://hdl.handle.net/10541/74014
DOI:
10.1182/blood-2008-04-152017
PubMed ID:
19264921
Type:
Article
Language:
en
ISSN:
1528-0020
Appears in Collections:
All Paterson Institute for Cancer Research; Stem Cell and Haematopoiesis; Stem Cell Biology

Full metadata record

DC FieldValue Language
dc.contributor.authorPerez-Campo, Flor-Maria-
dc.contributor.authorBorrow, Julian-
dc.contributor.authorKouskoff, Valerie-
dc.contributor.authorLacaud, Georges-
dc.date.accessioned2009-07-15T16:08:05Z-
dc.date.available2009-07-15T16:08:05Z-
dc.date.issued2009-05-14-
dc.identifier.citationThe histone acetyl transferase activity of monocytic leukemia zinc finger is critical for the proliferation of hematopoietic precursors. 2009, 113 (20):4866-74 Blooden
dc.identifier.issn1528-0020-
dc.identifier.pmid19264921-
dc.identifier.doi10.1182/blood-2008-04-152017-
dc.identifier.urihttp://hdl.handle.net/10541/74014-
dc.description.abstractThe monocytic leukemia zinc finger (MOZ) gene encodes a large multidomain protein that contains, besides other domains, 2 coactivation domains for the transcription factor Runx1/acute myeloid leukemia 1 and a histone acetyl transferase (HAT) catalytic domain. Recent studies have demonstrated the critical requirement for the complete MOZ protein in hematopoietic stem cell development and maintenance. However, the specific function of the HAT activity of MOZ remains unknown, as it has been shown that MOZ HAT activity is not required either for its role as Runx1 coactivator or for the leukemic transformation induced by MOZ transcriptional intermediary factor 2 (TIF2). To assess the specific requirement for this HAT activity during hematopoietic development, we have generated embryonic stem cells and mouse lines carrying a point mutation that renders the protein catalytically inactive. We report in this study that mice exclusively lacking the HAT activity of MOZ exhibit significant defects in the number of hematopoietic stem cells and hematopoietic committed precursors as well as a defect in B-cell development. Furthermore, we demonstrate that the failure to maintain a normal number of hematopoietic precursors is caused by the inability of HAT(-/-) cells to expand. These results indicate a specific role of MOZ-driven acetylation in controlling a desirable balance between proliferation and differentiation during hematopoiesis.en
dc.language.isoenen
dc.subjectLeukaemiaen
dc.subjectHaematopoiesisen
dc.subject.meshAnimals-
dc.subject.meshB-Lymphocytes-
dc.subject.meshCell Differentiation-
dc.subject.meshCell Lineage-
dc.subject.meshCell Proliferation-
dc.subject.meshEmbryo, Mammalian-
dc.subject.meshEnzyme Activation-
dc.subject.meshFemale-
dc.subject.meshHematopoiesis-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHistone Acetyltransferases-
dc.subject.meshMice-
dc.subject.meshMice, Knockout-
dc.subject.meshMutation-
dc.subject.meshPregnancy-
dc.subject.meshProtein Structure, Tertiary-
dc.titleThe histone acetyl transferase activity of monocytic leukemia zinc finger is critical for the proliferation of hematopoietic precursors.en
dc.typeArticleen
dc.contributor.departmentPaterson Institute for Cancer Research, University of Manchester, USA.en
dc.identifier.journalBlooden

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.