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 poly merase (pol) II through protein acetylation. While the physiological s ubstrates for those acetylases are poorly defined, possible targets in clude general transcription factors, activator proteins and histones. Using a cell-free system to reconstitute chromatin with increased hist one acetylation levels, we directly tested for a causal role of histon e acetylation in transcription by RNA pol II. Chromatin, containing ei ther control or acetylated histones, was reconstituted to comparable n ucleosome densities and characterized by electron microscopy after pso ralen cross-linking as well as by in vitro transcription. While HI-con taining control chromatin severely repressed transcription of our mode l hsp26 gene, highly acetylated chromatin was significantly less repre ssive, Acetylation of histones, and particularly of histone H4, affect ed transcription at the level of initiation. Monitoring the ability of the transcription machinery to associate with the promoter in chromat in, we found that heat shock factor, a crucial regulator of heat shock gene transcription, profited most from histone acetylation. These exp eriments demonstrate that histone acetylation can modulate activator a ccess to their target sites in chromatin, and provide a causal link be tween histone acetylation and enhanced transcription initiation of RNA pol II in chromatin.