An insulator embedded in the chicken α-globin locus regulates chromatin domain configuration and differential gene expression.
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.
Furlan-Magaril
Mayra
M
Instituto de Fisiología Celular, Departamento de Genética Molecular, Universidad Nacional Autónoma de México, México D.F., México.
Rebollar
Eria
E
Guerrero
Georgina
G
Fernández
Almudena
A
Moltó
Eduardo
E
González-Buendía
Edgar
E
Cantero
Marta
M
Montoliu
Lluís
L
Recillas-Targa
Félix
F
D000818:Animals; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002454:Cell Differentiation; D002460:Cell Line; D002645:Chickens / Q000235:genetics; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055012:Chromosomal Position Effects; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D056426:Genetic Loci; D038101:Insulator Elements; D019901:Locus Control Region; D051379:Mice; D008822:Mice, Transgenic; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012097:Repressor Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D055542:alpha-Globins / Q000235:genetics* / Q000378:metabolism
D000076246:CCCTC-Binding Factor; D002843:Chromatin; C000619698:Ctcf protein, mouse; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012097:Repressor Proteins; D055542:alpha-Globins
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