USF and NF-E2 cooperate to regulate the recruitment and activity of RNA polymerase II in the beta-globin gene locus.
The human beta-globin gene is expressed at high levels in erythroid cells and regulated by proximal and distal cis-acting DNA elements, including promoter, enhancer, and a locus control region (LCR). Transcription complexes are recruited not only to the globin gene promoters but also to the LCR. Previous studies have implicated the ubiquitously expressed transcription factor USF and the tissue-restricted activator NF-E2 in the recruitment of transcription complexes to the beta-globin gene locus. Here we demonstrate that although USF is required for the efficient association of RNA polymerase II (Pol II) with immobilized LCR templates, USF and NF-E2 together regulate the association of Pol II with the adult beta-globin gene promoter. Recruitment of Pol II to the LCR occurs in undifferentiated murine erythroleukemia cells, but phosphorylation of LCR-associated Pol II at serine 5 of the C-terminal domain is mediated by erythroid differentiation and requires the activity of NF-E2. Furthermore, we provide evidence showing that USF interacts with NF-E2 in erythroid cells. The data provide mechanistic insight into how ubiquitous and tissue-restricted transcription factors cooperate to regulate the recruitment and activity of transcription complexes in a tissue-specific chromatin domain.
Department of Biochemistry and Molecular Biology, Powell Gene Therapy Center, Center for Epigenetics, and Genetics Institute, University of Florida, Gainesville, Florida 32610, USA.
Zhuo
Z
Zhou
Xingguo
X
Li
Changwang
C
Deng
Paul A
PA
Ney
Suming
S
Huang
Jörg
J
Bungert
D000818:Animals; D045744:Cell Line, Tumor; D056426:Genetic Loci / Q000502:physiology*; D006801:Humans; D019901:Locus Control Region / Q000502:physiology*; D051379:Mice; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D055544:beta-Globins / Q000096:biosynthesis* / Q000235:genetics
D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; C494693:Nfe2 protein, mouse; D055544:beta-Globins; D012319:RNA Polymerase II