Show simple item record

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.
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
html.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.


This item appears in the following Collection(s)

Show simple item record