Distinct Mechanisms Control RNA Polymerase II Recruitment to a Tissue-Specific Locus Control Region and a Downstream Promoter

• Published in: Molecular cell 2001-08, Vol.8 (2), p.465-471
• Main Authors: Johnson, Kirby D., Christensen, Heather M., Zhao, Bryan, Bresnick, Emery H.
• Format: Article
• Language: English
• Subjects: Acetylation; Animals; DNA-Binding Proteins - metabolism; Erythroid-Specific DNA-Binding Factors; Globins - genetics; Histones - metabolism; Immunoblotting; locus control region; Locus Control Region - genetics; Mice; NF-E2 Transcription Factor, p45 Subunit; Precipitin Tests; Promoter Regions, Genetic - physiology; RNA Polymerase II - metabolism; Transcription Factors - metabolism; Tumor Cells, Cultured
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(01)00309-4

Histone acetylation precedes activation of many genes. However, the establishment and consequences of long-range acetylation patterns are poorly understood. To define molecular determinants of the developmentally dynamic histone acetylation pattern of the β-globin locus, we compared acetylation of the locus in MEL and CB3 erythroleukemia cells. CB3 cells lack the β-globin locus control region (LCR) binding protein p45/NF-E2. We found that p45/NF-E2 was required for histone hyperacetylation at adult β-globin promoters ∼50 kilobases downstream of the LCR, but not at the LCR. Surprisingly, RNA polymerase II associated with the LCR in a p45/NF-E2-independent manner, while its recruitment to the promoter required p45/NF-E2. We propose that polymerase accesses the LCR and p45/NF-E2 induces long-range transfer of polymerase to the promoter, resulting in transcriptional activation.