title: A novel chromatin insulator regulates the chicken folate receptor gene from the influence of nearby constitutive heterochromatin and the β-globin locus.
abstract: The three-dimensional architecture of genomes provides new insights about genome organization and function, but many aspects remain unsolved at the local genomic scale. Here we investigate the regulation of two erythroid-specific loci, a folate receptor gene (FOLR1) and the β-globin gene cluster, which are separated by 16kb of constitutive heterochromatin. We found that in early erythroid differentiation the FOLR1 gene presents a permissive chromatin configuration that allows its expression. Once the transition to the next differentiation state occurs, the heterochromatin spreads into the FOLR1 domain, concomitant with the dissociation of CTCF from a novel binding site, thereby resulting in irreversible silencing of the FOLR1 gene. We demonstrate that the sequences surrounding the CTCF-binding site possess classical insulator properties in vitro and in vivo. In contrast, the chicken cHS4 β-globin insulator present on the other side of the heterochromatic segment is in a constitutive open chromatin configuration, with CTCF constantly bound from the early stages of erythroid differentiation. Therefore, this study demonstrates that the 16kb of constitutive heterochromatin contributes to silencing of the FOLR1 gene during erythroid differentiation.
authors.affiliation: Instituto de Fisiología Celular, Departamento de Genética Molecular, Universidad Nacional Autónoma de México, Ciudad de México, D.F., Mexico.
authors.forename: Edgar
authors.initials: E
authors.lastname: González-Buendía
authors.affiliation: Instituto de Fisiología Celular, Departamento de Genética Molecular, Universidad Nacional Autónoma de México, Ciudad de México, D.F., Mexico; Department of Biochemistry and Molecular Biophysics, Mortimer B. Zuckerman Mind, Brain, and Behavior Institute, Columbia University, NY, USA.
authors.forename: Martín
authors.initials: M
authors.lastname: Escamilla-Del-Arenal
authors.affiliation: Instituto de Fisiología Celular, Departamento de Genética Molecular, Universidad Nacional Autónoma de México, Ciudad de México, D.F., Mexico.
authors.forename: Rosario
authors.initials: R
authors.lastname: Pérez-Molina
authors.affiliation: Centro Andaluz de Biología del Desarrollo, CSIC-Universidad Pablo de Olavide, Campus UPO, Sevilla, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Tena
authors.affiliation: Instituto de Fisiología Celular, Departamento de Genética Molecular, Universidad Nacional Autónoma de México, Ciudad de México, D.F., Mexico.
authors.forename: Georgina
authors.initials: G
authors.lastname: Guerrero
authors.affiliation: Instituto de Fisiología Celular, Departamento de Genética Molecular, Universidad Nacional Autónoma de México, Ciudad de México, D.F., Mexico.
authors.forename: Fernando
authors.initials: F
authors.lastname: Suaste-Olmos
authors.affiliation: Instituto de Fisiología Celular, Departamento de Genética Molecular, Universidad Nacional Autónoma de México, Ciudad de México, D.F., Mexico.
authors.forename: Erandi
authors.initials: E
authors.lastname: Ayala-Ortega
authors.affiliation: Centro Andaluz de Biología del Desarrollo, CSIC-Universidad Pablo de Olavide, Campus UPO, Sevilla, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Gómez-Skarmeta
authors.affiliation: Instituto de Fisiología Celular, Departamento de Genética Molecular, Universidad Nacional Autónoma de México, Ciudad de México, D.F., Mexico. Electronic address: frecilla@ifc.unam.mx.
authors.forename: Félix
authors.initials: F
authors.lastname: Recillas-Targa
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002461:Cell Line, Transformed; D002642:Chick Embryo; D002645:Chickens; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics; D058975:Folate Receptor 1 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D038101:Insulator Elements / Q000502:physiology*; D055544:beta-Globins / Q000235:genetics*
chemical_list: D002843:Chromatin; D058975:Folate Receptor 1; D006570:Heterochromatin; D055544:beta-Globins
keywords: CTCF; Chromatin insulator; DNA methylation; Folate receptor and globin genes; Heterochromatin; Transcription