Chicken alpha-globin switching depends on autonomous silencing of the embryonic pi globin gene by epigenetics mechanisms.
Switching in hemoglobin gene expression is an informative paradigm for studying transcriptional regulation. Here we determined the patterns of chicken alpha-globin gene expression during development and erythroid differentiation. Previously published data suggested that the promoter regions of alpha-globin genes contain the complete information for proper developmental regulation. However, our data show a preferential trans-activation of the embryonic alpha-globin gene independent of the developmental or differentiation stage. We also found that DNA methylation and histone deacetylation play key roles in silencing the expression of the embryonic pi gene in definitive erythrocytes. However, drug-mediated reactivation of the embryonic gene during definitive erythropoiesis dramatically impaired the expression of the adult genes, suggesting gene competition or interference for enhancer elements. Our results also support a model in which the lack of open chromatin marks and localized recruitment of chicken MeCP2 contribute to autonomous gene silencing of the embryonic alpha-globin gene in a developmentally specific manner. We propose that epigenetic mechanisms are necessary for in vivo chicken alpha-globin gene switching through differential gene silencing of the embryonic alpha-globin gene in order to allow proper activation of adult alpha-globin genes.
Rincón-Arano
Héctor
H
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-242, México 04510, DF, México.
Guerrero
Georgina
G
Valdes-Quezada
Christian
C
Recillas-Targa
Félix
F
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects; D004742:Enhancer Elements, Genetic / Q000235:genetics; D041905:Erythroid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics; D050982:GATA1 Transcription Factor / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D055554:Hemoglobin Subunits / Q000235:genetics* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D055542:alpha-Globins / Q000235:genetics*
D050982:GATA1 Transcription Factor; D055554:Hemoglobin Subunits; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D051783:Methyl-CpG-Binding Protein 2; D055542:alpha-Globins