TY - JOUR
T1 - cMYB is involved in the regulation of fetal hemoglobin production in adults
AU - Jiang, J
AU - Best, S
AU - Menzel, S
AU - Silver, N
AU - Lai, M I
AU - Surdulescu, G L
AU - Spector, T D
AU - Thein, S L
PY - 2006/8/1
Y1 - 2006/8/1
N2 - A quantitative trait locus (QTL) controlling HbF levels has previously been mapped to chromosome 6q23 in an Asian-Indian kindred with beta thalassemia and helerocellular 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
AB - A quantitative trait locus (QTL) controlling HbF levels has previously been mapped to chromosome 6q23 in an Asian-Indian kindred with beta thalassemia and helerocellular 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
U2 - 10.1182/blood-2006-01-008912
DO - 10.1182/blood-2006-01-008912
M3 - Article
SN - 1528-0020
VL - 108
SP - 1077
EP - 1083
JO - Blood
JF - Blood
IS - 3
ER -