An insulator embedded in the chicken α-globin locus regulates chromatin domain configuration and differential gene expression
| Autor: | Almudena Fernández, Marta Cantero, Mayra Furlan-Magaril, Georgina Guerrero, Lluís Montoliu, Félix Recillas-Targa, Eria A. Rebollar, Edgar González-Buendía, Eduardo Moltó |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Transcriptional Activation
CCCTC-Binding Factor Transcription Genetic Cellular differentiation Mice Transgenic Biology Gene Regulation Chromatin and Epigenetics Poly(ADP-ribose) Polymerase Inhibitors Transfection Cell Line Chromosomal Position Effects Mice Erythroid Cells alpha-Globins Gene expression Genetics Animals ChIA-PET Locus control region Regulation of gene expression Binding Sites Cell Differentiation Locus Control Region Chromatin Repressor Proteins Gene Expression Regulation CTCF Genetic Loci Insulator Elements Chickens |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Genome organization into transcriptionally active domains denotes one of the first levels of gene expression regulation. Although the chromatin domain concept is generally accepted, only little is known on how domain organization impacts the regulation of differential gene expression. Insulators might hold answers to address this issue as they delimit and organize chromatin domains. We have previously identified a CTCF-dependent insulator with enhancer-blocking activity embedded in the 5' non-coding region of the chicken α-globin domain. Here, we demonstrate that this element, called the αEHS-1.4 insulator, protects a transgene against chromosomal position effects in stably transfected cell lines and transgenic mice. We found that this insulator can create a regulated chromatin environment that coincides with the onset of adult α-globin gene expression. Furthermore, such activity is in part dependent on the in vivo regulated occupancy of CTCF at the αEHS-1.4 element. Insulator function is also regulated by CTCF poly(ADP-ribosyl)ation. Our results suggest that the αEHS-1.4 insulator contributes in organizing the chromatin structure of the α-globin gene domain and prevents activation of adult α-globin gene expression at the erythroblast stage via CTCF. |
| Databáze: | OpenAIRE |
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