Document Detail


The transcription factor B-Myb is essential for S-phase progression and genomic stability in diploid and polyploid megakaryocytes.
MedLine Citation:
PMID:  16551698     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cell-cycle-regulated Myb-family transcription factor B-Myb is crucial during S phase in many diploid cell types. We have examined the expression and function of B-Myb in megakaryocytic differentiation, during which cells progress from a diploid to a polyploid state. In contrast to terminal differentiation of most haematopoietic cells, during which B-myb is rapidly downregulated, differentiation of megakaryocytes is accompanied by continued B-myb RNA and protein expression. Overexpression of B-Myb in a megakaryoblastic cell line resulted in an increase in the number of cells entering S phase and, upon induction of differentiation, the fraction of cells actively endoreplicating increased. By contrast, reduction of B-Myb levels using short interfering (si)RNA resulted in a decline in S-phase progression during both normal and endoreplicative DNA synthesis. This effect correlated with aberrant localisation of initiation of DNA replication within the nucleus and an increased fraction of cells in mitosis. Chromosomal fragmentation and other aberrations, including shorter, thicker chromatids, end-to-end fusion, and loss of a chromatid, suggest that reduced B-Myb activity is also associated with structural chromosomal instability.
Authors:
Paloma García; Jon Frampton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-21
Journal Detail:
Title:  Journal of cell science     Volume:  119     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-04-06     Completed Date:  2006-08-22     Revised Date:  2007-08-13    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1483-93     Citation Subset:  IM    
Affiliation:
Institute for Biomedical Research, Birmingham University Medical School, Edgbaston, Birmingham, B15 2TT, UK.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle Proteins / physiology*
Cell Differentiation
Cell Line, Tumor
Cells, Cultured
Chromosomal Instability*
Chromosome Aberrations
DNA-Binding Proteins / physiology*
Diploidy
Down-Regulation
Genomic Instability*
Histones / metabolism
Humans
Megakaryocytes / metabolism*
Phosphorylation
Polyploidy
S Phase*
Trans-Activators / physiology*
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/Histones; 0/MYBL2 protein, human; 0/Trans-Activators

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