Document Detail


cMYB is involved in the regulation of fetal hemoglobin production in adults.
MedLine Citation:
PMID:  16861354     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A quantitative trait locus (QTL) controlling HbF levels has previously been mapped to chromosome 6q23 in an Asian-Indian kindred with beta thalassemia and heterocellular hereditary persistence of fetal hemoglobin (HPFH). Five protein-coding genes, ALDH8A1, HBS1L, cMYB, AHI1, and PDE7B reside in this 1.5-megabase (Mb) candidate interval of 6q23. To direct sequencing efforts we compared the expression profiles of these 5 genes between 12 individuals with elevated and 14 individuals with normal HbF levels during adult erythropoiesis by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Two genes, cMYB and HBS1L, demonstrated simultaneous transcriptional down-regulation in individuals with elevated HbF levels. Transfection of K562 cells encoding human cDNA of cMYB and HBS1L genes showed that, although overexpression of ectopic cMYB inhibited gamma-globin gene expression, overexpression of HBS1L had no effect. Low levels of cMYB were associated with low cell expansions, accelerated erythroid maturation, and higher number of macrophages in erythroid cell culture. These observations suggest that differences in the intrinsic levels of cMYB may account for some of the variation in adult HbF levels. The possible mechanism of cMYB influencing gamma- to beta-globin switching is discussed.
Authors:
Jie Jiang; Steve Best; Stephan Menzel; Nicholas Silver; Mei I Lai; Gabriela L Surdulescu; Tim D Spector; Swee Lay Thein
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Blood     Volume:  108     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-24     Completed Date:  2006-10-05     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1077-83     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Cell Count
Down-Regulation / genetics
Erythroid Cells
Erythropoiesis
Fetal Hemoglobin / biosynthesis*,  genetics
Gene Expression Regulation*
Humans
K562 Cells
Macrophages / cytology
Proto-Oncogene Proteins c-myb / physiology*
Transcription, Genetic
Transfection
Grant Support
ID/Acronym/Agency:
G0000111//Medical Research Council; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-myb; 9034-63-3/Fetal Hemoglobin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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