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Histone H3 tail positioning and acetylation by the c-Myb but not the v-Myb DNA-binding SANT domain

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Item Type:Article
Title:Histone H3 tail positioning and acetylation by the c-Myb but not the v-Myb DNA-binding SANT domain
Creators Name:Mo, X. and Kowenz-Leutz, E. and Laumonnier, Y. and Xu, H. and Leutz, A.
Abstract:The c-Myb transcription factor coordinates proliferation and differentiation of hematopoietic precursor cells. Myb has three consecutive N-terminal SANT-type repeat domains (R1, R2, R3), two of which (R2, R3) form the DNA-binding domain (DBD). Three amino acid substitutions in R2 alter the way Myb regulates genes and determine the leukemogenicity of the retrovirally transduced v-Myb oncogene. The molecular mechanism of how these mutations unleash the leukemogenic potential of Myb is unknown. Here we demonstrate that the c-Myb-DBD binds to the N-terminal histone tails of H3 and H3.3. C-Myb binding facilitates histone tail acetylation, which is mandatory during activation of prevalent differentiation genes in conjunction with CCAAT enhancer-binding proteins (C/EBP). Leukemogenic mutations in v-Myb eliminate the interaction with H3 and acetylation of H3 tails and abolish activation of endogenous differentiation genes. In primary v-myb-transformed myeloblasts, pharmacologic enhancement of H3 acetylation restored activation of differentiation genes and induced cell differentiation. Our data link a novel chromatin function of c-Myb with lineage-specific expression of differentiation genes and relate the loss of this function with the leukemic conversion of Myb.
Keywords:chromatin, Hematopoiesis, Leukemia, Myb, Transcription, Animals, Chickens
Source:Genes & Development
ISSN:0890-9369
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Volume:19
Number:20
Page Range:2447-2457
Date:29 September 2005
Official Publication:https://doi.org/10.1101/gad.355405
PubMed:View item in PubMed

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