YY1 and GATA-1 interaction modulate the chicken 3'-side alpha-globin enhancer activity.
Studying the chicken alpha-globin domain as a model system of gene regulation, we have previously identified contiguous silencer-enhancer elements located on the 3'-side of the domain. To better characterize the enhancer we performed a systematic functional analysis to define its expression influence range and the ubiquitous and stage-specific transcriptional regulators interacting with this control element. In contrast to previous reports, we found that, in addition to a core element that includes three GATA-1 binding sites, the enhancer incorporates a 120 base-pair DNA fragment where EKLF, NF-E2 and a fourth GATA-1 factor could interact. Functional experiments demonstrate that the enhancer activity over the adult alpha(D) promoter is differentially regulated. We found that the transcriptional factor Ying Yang 1 (YY1) binds to the 120 base-pair DNA fragment and its effect over the enhancer activity is GATA-1-dependent. In addition, we characterize a novel physical interaction between GATA-1 and YY1 that influences the enhancer function. Experiments using a histone deacetylation inhibitor indicate that, in pre-erythroblasts, the enhancer down-regulation could be influenced by a closed chromatin conformation. Our observations show that the originally defined enhancer possesses a more complex composition than previously assumed. We propose that its activity is modulated through differential nuclear factor interactions and chromatin modifications at distinct erythroid stages.
Rincón-Arano
Héctor
H
Instituto de Fisiología Celular, Departamento de Genética Molecular, Universidad Nacional Autónoma de México, Apartado Postal 70-242, México D.F. 04510, México.
Valadez-Graham
Viviana
V
Guerrero
Georgina
G
Escamilla-Del-Arenal
Martín
M
Recillas-Targa
Félix
F
D024509:3' Flanking Region; D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D004900:Erythroblasts / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D005914:Globins / Q000235:genetics*; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology; D051741:Kruppel-Like Transcription Factors; D050983:NF-E2 Transcription Factor; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics*; D050986:YY1 Transcription Factor
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D051741:Kruppel-Like Transcription Factors; D050983:NF-E2 Transcription Factor; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C080774:erythroid Kruppel-like factor; C012589:trichostatin A; D005914:Globins