Independent formation of DnaseI hypersensitive sites in the murine beta-globin locus control region.

Abstract:

:Mammalian beta-globin loci are composed of multiple orthologous genes whose expression is erythroid specific and developmentally regulated. The expression of these genes both from the endogenous locus and from transgenes is strongly influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive sites (HSs) known as the locus control region (LCR). The LCR encompasses 5 major HSs, each of which is highly homologous among humans, mice, and other mammals. To analyze the function of individual HSs in the endogenous murine beta-globin LCR, we have used homologous recombination in embryonic stem cells to produce 5 mouse lines, each of which is deficient for 1 of these major HSs. In this report, we demonstrate that deletion of the conserved region of 5'HS 1, 2, 3, 4, or 5/6 abolishes HS formation at the deletion site but has no influence on the formation of the remaining HSs in the LCR. Therefore, in the endogenous murine locus, there is no dominant or initiating site whose formation must precede the formation of the other HSs. This is consistent with the idea that HSs form autonomously. We discuss the implications of these findings for current models of beta-globin regulation.

journal_name

Blood

journal_title

Blood

authors

Bender MA,Mehaffey MG,Telling A,Hug B,Ley TJ,Groudine M,Fiering S

subject

Has Abstract

pub_date

2000-06-01 00:00:00

pages

3600-4

issue

11

eissn

0006-4971

issn

1528-0020

journal_volume

95

pub_type

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