Binding of disparate transcriptional activators to nucleosomal DNA is inherently cooperative
- 1 March 1995
- journal article
- research article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 15 (3) , 1405-1421
- https://doi.org/10.1128/mcb.15.3.1405
Abstract
To investigate mechanisms by which multiple transcription factors access complex promoters and enhancers within cellular chromatin, we have analyzed the binding of disparate factors to nucleosome cores. We used a purified in vitro system to analyze binding of four activator proteins, two GAL4 derivatives, USF, and NF-kappa B (KBF1), to reconstituted nucleosome cores containing different combinations of binding sites. Here we show that binding of any two or all three of these factors to nucleosomal DNA is inherently cooperative. Thus, the binuclear Zn clusters of GAL4, the helix-loop-helix/basic domains of USF, and the rel domain of NF-kappa B all participated in cooperative nucleosome binding, illustrating that this effect is not restricted to a particular DNA-binding domain. Simultaneous binding by two factors increased the affinity of individual factors for nucleosomal DNA by up to 2 orders of magnitude. Importantly, cooperative binding resulted in efficient nucleosome binding by factors (USF and NF-kappa B) which independently possess little nucleosome-binding ability. The participation of GAL4 derivatives in cooperative nucleosome binding required only DNA-binding and dimerization domains, indicating that disruption of histone-DNA contacts by factor binding was responsible for the increased affinity of additional factors. Cooperative nucleosome binding required sequence-specific binding of all transcription factors, appeared to have spatial constraints, and was independent of the orientation of the binding sites on the nucleosome. These results indicate that cooperative nucleosome binding is a general mechanism that may play a significant role in loading complex enhancer and promoter elements with multiple diverse factors in chromatin and contribute to the generation of threshold responses and transcriptional synergy by multiple activator sites in vivo.Keywords
This publication has 95 references indexed in Scilit:
- Nucleosome disruption and enhancement of activator binding by a human SW1/SNF complexNature, 1994
- The role of activators in assembly of RNA polymerase II transcription complexesCurrent Opinion in Genetics & Development, 1994
- Nucleosome Disruption by Transcription Factor Binding in YeastScience, 1993
- GAL4 disrupts a repressing nucleosome during activation of GAL1 transcription in vivo.Genes & Development, 1993
- Histones, nucleosomes and transcriptionCurrent Opinion in Genetics & Development, 1993
- Nucleosome Core Displacement in Vitro via a Metastable Transcription Factor-Nucleosome ComplexScience, 1992
- Transcription Factor Loading on the MMTV Promoter: A Bimodal Mechanism for Promoter ActivationScience, 1992
- Co-operative binding of the glucocorticoid receptor DNA binding domain is one of at least two mechanisms for synergismJournal of Molecular Biology, 1991
- Nucleosome positioning modulates accessibility of regulatory proteins to the mouse mammary tumor virus promoterCell, 1990
- Synergism of closely adjacent estrogen-responsive elements increases their regulatory potentialJournal of Molecular Biology, 1988