Mechanism of transcriptional antirepression by GAL4-VP16.
Promoter- and enhancer-binding factors appear to function by facilitating the transcription reaction as well as by counteracting chromatin-mediated repression (antirepression). We have examined the mechanism by which a hybrid activator, GAL4-VP16, is able to counteract histone H1-mediated repression by using both H1-DNA complexes and reconstituted H1-containing chromatin templates. The GAL4 DNA binding domain alone was sufficient to disrupt local H1-DNA interactions, but a transcriptional region was additionally necessary for antirepression. GAL4-VP16-mediated antirepression required an auxiliary factor, denoted as a co-antirepressor, which was partially purified from Drosophila embryos. We have found that the co-antirepressor activity was sensitive to digestion with RNase A. Moreover, total RNA from Drosophila embryos could partially substitute for the co-antirepressor fraction, which indicated that the co-antirepressor may function as a histone acceptor ("histone sink"). These findings suggest a model for gene activation in which sequence-specific transcription factors disrupt H1-DNA interactions at the promoter to facilitate transfer of H1 to a histone acceptor, which then allows access of the basal transcription factors to the DNA template.
Croston
G E
GE
Department of Biology, University of California, San Diego, La Jolla 92093.
Laybourn
P J
PJ
Paranjape
S M
SM
Kadonaga
J T
JT
D000818:Animals; D002843:Chromatin / Q000502:physiology; D004247:DNA / Q000502:physiology; D003850:Deoxyribonuclease I; D004330:Drosophila; D004742:Enhancer Elements, Genetic; D005656:Fungal Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006657:Histones / Q000502:physiology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013698:Templates, Genetic; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D002843:Chromatin; D005656:Fungal Proteins; C070633:Gal-VP16; D006657:Histones; D015534:Trans-Activators; D004247:DNA; D003850:Deoxyribonuclease I