A novel chromatin insulator regulates the chicken folate receptor gene from the influence of nearby constitutive heterochromatin and the β-globin locus
| Autor: | Martín Escamilla-Del-Arenal, Rosario Pérez-Molina, Félix Recillas-Targa, José Luis Gómez-Skarmeta, Georgina Guerrero, Fernando Suaste-Olmos, Juan J. Tena, Erandi Ayala-Ortega, Edgar González-Buendía |
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| Přispěvatelé: | Universidad Nacional Autónoma de México, Consejo Nacional de Ciencia y Tecnología (México), Junta de Andalucía, Universidad Pablo de Olavide, Ministerio de Economía y Competitividad (España) |
| Rok vydání: | 2015 |
| Předmět: |
Euchromatin
Heterochromatin Biophysics Folate receptor and globin genes Chick Embryo beta-Globins Biology Insulator (genetics) Biochemistry Structural Biology Gene cluster Genetics Constitutive heterochromatin Animals Erythropoiesis Folate Receptor 1 Chromatin insulator Molecular Biology Cell Line Transformed DNA methylation Cell Differentiation CTCF Chromatin Gene Expression Regulation Genetic Loci Heterochromatin protein 1 Insulator Elements Chickens Transcription |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1874-9399 |
| Popis: | 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 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. This 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. |
| Databáze: | OpenAIRE |
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