The binding of a Fos/Jun heterodimer can completely disrupt the structure of a nucleosome.
An important first step in the chromatin remodelling process is the initial binding of a transcriptional activator to a nucleosomal template. We have investigated the ability of Fos/Jun (a transcriptional activator involved in the signal transduction pathway) to interact with its cognate binding site located in the promoter region of the mouse fos-related antigen-2 (fra-2) promoter, when this site was reconstituted into a nucleosome. Two different nucleosome assembly systems were employed to assemble principally non-acetylated or acetylated nucleosomes. The ability of Fos/Jun to interact with an acetylated or an unacetylated nucleosome differed markedly. Fos/Jun bound to an unacetylated nucleosome with only a 4- to 5-fold reduction in DNA binding affinity compared with naked DNA. Strikingly, the binding of Fos/Jun to a single high-affinity site incorporated into an acetylated nucleosome resulted in the complete disruption of nucleosomal structure without histone displacement. Moreover, this disruption was sufficient to facilitate the subsequent binding of a second transcription factor.
Ng
K W
KW
Division of Biochemistry, The John Curtin School of Medical Research, The Australian National University, Canberra.
Ridgway
P
P
Cohen
D R
DR
Tremethick
D J
DJ
D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D002645:Chickens; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D051921:Fos-Related Antigen-2; D006657:Histones / Q000378:metabolism; D016350:Leucine Zippers; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D009707:Nucleosomes / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D051876:Sex-Determining Region Y Protein; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014982:Xenopus laevis; D000099169:Fos-Related Antigen 1
D004247:DNA; D004268:DNA-Binding Proteins; D051921:Fos-Related Antigen-2; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D051876:Sex-Determining Region Y Protein; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000099169:Fos-Related Antigen 1; C497873:Fosl2 protein, mouse; C497874:Fosl2 protein, rat