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dc.contributor.authorTena, Juan J.-
dc.contributor.authorGómez-Skarmeta, José Luis-
dc.contributor.authorRecillas-Targa, Félix-
dc.identifierdoi: 10.1016/j.bbagrm.2015.05.011-
dc.identifierissn: 1874-9399-
dc.identifier.citationBiochimica et Biophysica Acta - Gene Regulatory Mechanisms 1849(8): 955-965 (2015)-
dc.description.abstractThe 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 16. kb 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 16. kb of constitutive heterochromatin contributes to silencing of the FOLR1 gene during erythroid differentiation.-
dc.description.sponsorshipThis work was supported by the DGAPA-PAPIIT, UNAM (IN209403, IN203811 and IN201114), and CONACyT (42653-Q, 128464 and 220503) to FR-T, and by a Ph.D. fellowship from CONACyT (CVU 207989) and Programa de Apoyo a los Estudios del Posgrado (PAEP), UNAM to EG-B. Additional support was provided by the PhD Graduate Program, “Doctorado en Ciencias Bioquímicas”, to the Instituto de Fisiología Celular and the Universidad Nacional Autónoma de México. JLG-S was funded by grants from Ministerio de Economía y Competitividad (BFU2013-41322-P) and the Andalusian Government (BIO-396). A postdoctoral grant from the Universidad Pablo de Olavide supported JJT.-
dc.subjectDNA methylation-
dc.subjectFolate receptor and globin genes-
dc.subjectChromatin insulator-
dc.titleA novel chromatin insulator regulates the chicken folate receptor gene from the influence of nearby constitutive heterochromatin and the β-globin locus-
dc.description.versionPeer Reviewed-
dc.contributor.funderUniversidad Nacional Autónoma de México-
dc.contributor.funderConsejo Nacional de Ciencia y Tecnología (México)-
dc.contributor.funderJunta de Andalucía-
dc.contributor.funderUniversidad Pablo de Olavide-
dc.contributor.funderMinisterio de Economía y Competitividad (España)-
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