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Publication : High Fractional Occupancy of a Tandem Maf Recognition Element and Its Role in Long-Range β-Globin Gene Regulation.

First Author  Stees JR Year  2015
Journal  Mol Cell Biol Volume  36
Issue  2 Pages  238-50
PubMed ID  26503787 Mgi Jnum  J:235915
Mgi Id  MGI:5803940 Doi  10.1128/MCB.00723-15
Citation  Stees JR, et al. (2015) High Fractional Occupancy of a Tandem Maf Recognition Element and Its Role in Long-Range beta-Globin Gene Regulation. Mol Cell Biol 36(2):238-50
abstractText  Enhancers and promoters assemble protein complexes that ultimately regulate the recruitment and activity of RNA polymerases. Previous work has shown that at least some enhancers form stable protein complexes, leading to the formation of enhanceosomes. We analyzed protein-DNA interactions in the murine beta-globin gene locus using the methyltransferase accessibility protocol for individual templates (MAPit). The data show that a tandem Maf recognition element (MARE) in locus control region (LCR) hypersensitive site 2 (HS2) reveals a remarkably high degree of occupancy during differentiation of mouse erythroleukemia cells. Most of the other transcription factor binding sites in LCR HS2 or in the adult beta-globin gene promoter regions exhibit low fractional occupancy, suggesting highly dynamic protein-DNA interactions. Targeting of an artificial zinc finger DNA-binding domain (ZF-DBD) to the HS2 tandem MARE caused a reduction in the association of MARE-binding proteins and transcription complexes at LCR HS2 and the adult betamajor-globin gene promoter but did not affect expression of the betaminor-globin gene. The data demonstrate that a stable MARE-associated footprint in LCR HS2 is important for the recruitment of transcription complexes to the adult betamajor-globin gene promoter during erythroid cell differentiation.
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