Histone acetylation facilitates RNA polymerase II transcription of the Drosophila hsp26 gene in chromatin.
A number of activators are known to increase transcription by RNA polymerase (pol) II through protein acetylation. While the physiological substrates for those acetylases are poorly defined, possible targets include general transcription factors, activator proteins and histones. Using a cell-free system to reconstitute chromatin with increased histone acetylation levels, we directly tested for a causal role of histone acetylation in transcription by RNA pol II. Chromatin, containing either control or acetylated histones, was reconstituted to comparable nucleosome densities and characterized by electron microscopy after psoralen cross-linking as well as by in vitro transcription. While H1-containing control chromatin severely repressed transcription of our model hsp26 gene, highly acetylated chromatin was significantly less repressive. Acetylation of histones, and particularly of histone H4, affected transcription at the level of initiation. Monitoring the ability of the transcription machinery to associate with the promoter in chromatin, we found that heat shock factor, a crucial regulator of heat shock gene transcription, profited most from histone acetylation. These experiments demonstrate that histone acetylation can modulate activator access to their target sites in chromatin, and provide a causal link between histone acetylation and enhanced transcription initiation of RNA pol II in chromatin.
Nightingale
K P
KP
Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
Wellinger
R E
RE
Sogo
J M
JM
Becker
P B
PB
D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000378:metabolism* / Q000648:ultrastructure; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D017344:Genes, Insect; D006360:Heat-Shock Proteins / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism*; D013698:Templates, Genetic; D014158:Transcription, Genetic
D002843:Chromatin; D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; D006657:Histones; C087442:Hsp26 protein, Drosophila; D012319:RNA Polymerase II