Distinct mechanisms control RNA polymerase II recruitment to a tissue-specific locus control region and a downstream promoter.
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 beta-globin locus, we compared acetylation of the locus in MEL and CB3 erythroleukemia cells. CB3 cells lack the beta-globin locus control region (LCR) binding protein p45/NF-E2. We found that p45/NF-E2 was required for histone hyperacetylation at adult beta-globin promoters approximately 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.
Johnson
K D
KD
University of Wisconsin Medical School, Department of Pharmacology, Molecular and Cellular Pharmacology Program, Madison, WI 53706, USA.
Christensen
H M
HM
Zhao
B
B
Bresnick
E H
EH
D000107:Acetylation; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D005914:Globins / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D015151:Immunoblotting; D019901:Locus Control Region / Q000235:genetics*; D051379:Mice; D050984:NF-E2 Transcription Factor, p45 Subunit; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012319:RNA Polymerase II / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D006657:Histones; D050984:NF-E2 Transcription Factor, p45 Subunit; D014157:Transcription Factors; D005914:Globins; D012319:RNA Polymerase II