title: cMYB is involved in the regulation of fetal hemoglobin production in adults.
abstract: 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.affiliation: Department of Haematological Medicine, King's College London School of Medicine at King's College Hospital, Denmark Hill Campus, London SE5 9PJ, United Kingdom.
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.forename: Steve
authors.initials: S
authors.lastname: Best
authors.forename: Stephan
authors.initials: S
authors.lastname: Menzel
authors.forename: Nicholas
authors.initials: N
authors.lastname: Silver
authors.forename: Mei I
authors.initials: MI
authors.lastname: Lai
authors.forename: Gabriela L
authors.initials: GL
authors.lastname: Surdulescu
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.forename: Swee Lay
authors.initials: SL
authors.lastname: Thein
mesh_terms: D000328:Adult; D002452:Cell Count; D015536:Down-Regulation / Q000235:genetics; D041905:Erythroid Cells; D004920:Erythropoiesis; D005319:Fetal Hemoglobin / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D020014:K562 Cells; D008264:Macrophages / Q000166:cytology; D020598:Proto-Oncogene Proteins c-myb / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D020598:Proto-Oncogene Proteins c-myb; D005319:Fetal Hemoglobin