Linear distance from the locus control region determines epsilon-globin transcriptional activity.

Abstract:

:Enhancer elements modulate promoter activity over vast chromosomal distances, and mechanisms that ensure restrictive interactions between promoters and enhancers are critical for proper control of gene expression. The human beta-globin locus control region (LCR) activates expression of five genes in erythroid cells, including the proximal embryonic epsilon- and the distal adult beta-globin genes. To test for possible distance sensitivity of the genes to the LCR, we extended the distance between the LCR and genes by 2.3 kbp within the context of a yeast artificial chromosome, followed by the generation of transgenic mice (TgM). In these TgM lines, epsilon-globin gene expression decreased by 90%, while the more distantly located gamma- or beta-globin genes were not affected. Remarkably, introduction of a consensus EKLF binding site into the epsilon-globin promoter rendered its expression distance insensitive; when tested in an EKLF-null genetic background, expression of the mutant epsilon-globin gene was severely compromised. Thus, the epsilon-globin gene differs in its distance sensitivity to the LCR from the other beta-like globin genes, which is, at least in part, determined by the transcription factor EKLF.

journal_name

Mol Cell Biol

authors

Shimotsuma M,Matsuzaki H,Tanabe O,Campbell AD,Engel JD,Fukamizu A,Tanimoto K

doi

10.1128/MCB.00602-07

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

5664-72

issue

16

eissn

0270-7306

issn

1098-5549

pii

MCB.00602-07

journal_volume

27

pub_type

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