title: CTCF demarcates chicken embryonic α-globin gene autonomous silencing and contributes to adult stage-specific gene expression.
abstract: Genomic loci composed of more than one gene are frequently subjected to differential gene expression, with the chicken α-globin domain being a clear example. In the present study we aim to understand the globin switching mechanisms responsible for the epigenetic silencing of the embryonic π gene and the transcriptional activation of the adult α(D) and α(A) genes at the genomic domain level. In early stages, we describe a physical contact between the embryonic π gene and the distal 3' enhancer that is lost later during development. We show that such a level of regulation is achieved through the establishment of a DNA hypermethylation sub-domain that includes the embryonic gene and the adjacent genomic sequences. The multifunctional CCCTCC-binding factor (CTCF), which is located upstream of the α(D) gene promoter, delimits this sub-domain and creates a transition between the inactive sub-domain and the active sub-domain, which includes the adult α(D) gene. In avian-transformed erythroblast HD3 cells that are induced to differentiate, we found active DNA demethylation of the adult α(D) promoter, coincident with the incorporation of 5-hydroxymethylcytosine (5hmC) and concomitant with adult gene transcriptional activation. These results suggest that autonomous silencing of the embryonic π gene is needed to facilitate an optimal topological conformation of the domain. This model proposes that CTCF is contributing to a specific chromatin configuration that is necessary for differential α-globin gene expression during development.
authors.affiliation: Instituto de Fisiología Celular; Departamento de Genética Molecular; Universidad Nacional Autónoma de México; México D.F., México.
authors.forename: Christian
authors.initials: C
authors.lastname: Valdes-Quezada
authors.forename: Cristian
authors.initials: C
authors.lastname: Arriaga-Canon
authors.forename: Yael
authors.initials: Y
authors.lastname: Fonseca-Guzmán
authors.forename: Georgina
authors.initials: G
authors.lastname: Guerrero
authors.forename: Félix
authors.initials: F
authors.lastname: Recillas-Targa
mesh_terms: D000818:Animals; D001483:Base Sequence; D000076246:CCCTC-Binding Factor; D002454:Cell Differentiation; D002642:Chick Embryo; D002843:Chromatin / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D047108:Embryonic Development / Q000235:genetics*; D044127:Epigenesis, Genetic; D041905:Erythroid Cells / Q000166:cytology; D005786:Gene Expression Regulation; D020868:Gene Silencing; D056426:Genetic Loci; D006657:Histones / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D055542:alpha-Globins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000076246:CCCTC-Binding Factor; D002843:Chromatin; D006657:Histones; D012097:Repressor Proteins; D055542:alpha-Globins
keywords: 5-hydroxymethylcytosine; CTCF; DNA methylation; chromosome conformation capture; enhancer-promoter interaction; epigenetic silencing