Recruitment of transcription complexes to the beta-globin gene locus in vivo and in vitro.
Erythroid-specific, high level expression of the beta-globin genes is regulated by the locus control region (LCR), composed of multiple DNase I-hypersensitive sites and located far upstream of the genes. Recent studies have shown that LCR core elements recruit RNA polymerase II (pol II). In the present study we demonstrate the following: 1) pol II and other basal transcription factors are recruited to LCR core hypersensitive elements; 2) pol II dissociates from and re-associates with the globin gene locus during replication; 3) pol II interacts with the LCR but not with the beta-globin gene prior to erythroid differentiation in embryonic stem cells; and 4) the erythroid transcription factor NF-E2 facilitates the transfer of pol II from immobilized LCR constructs to a beta-globin gene in vitro. The data are consistent with the hypothesis that the LCR serves as the primary attachment site for the recruitment of macromolecular complexes involved in chromatin structure alterations and transcription of the globin genes.
Vieira
Karen F
KF
Department of Biochemistry and Molecular Biology, Centers for Gene Therapy and Mammalian Genetics, College of Medicine, University of Florida, Gainesville, Florida 32610, USA.
Levings
Padraic P
PP
Hill
Meredith A
MA
Crusselle
Valerie J
VJ
Kang
Sung-Hae Lee
SH
Engel
James Douglas
JD
Bungert
Jörg
J
D000818:Animals; D004247:DNA / Q000378:metabolism*; D005914:Globins / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D051379:Mice; D012319:RNA Polymerase II / Q000378:metabolism; D013234:Stem Cells; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
D014157:Transcription Factors; D005914:Globins; D004247:DNA; D012319:RNA Polymerase II