Cooperation between Complexes that Regulate Chromatin Structure and Transcription

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/S0014-5793%2801%2903309-9

Bromodomain: an acetyl-lysine binding domain

https://www.gs.washington.edu/academics/courses/braun/55106/readings/agalioti.pdf

Ordered Recruitment of Chromatin Modifying and General Transcription Factors to the IFN-β Promoter

Histone acetylation and deacetylation in the yeast Saccharomyces cerevisiae occur by targeting acetyltransferase and deacetylase enzymes to gene promoters and, in an untargeted and global manner, by affecting most nucleosomes. Recently, new roles for histone acetylation have been uncovered, not only in transcription but also in DNA replication, repair and heterochromatin formation. Interestingly, specific acetylatable lysines can function as binding sites for regulatory factors. Moreover, histone deacetylation is not only repressive but can be required for gene activity.

Histone acetylation and deacetylation in yeast

Function and Selectivity of Bromodomains in Anchoring Chromatin-Modifying Complexes to Promoter Nucleosomes

The access of transcription factors to eukaryotic promoters often requires modification of their chromatin structure, which is accomplished by the action of two general classes of multiprotein complexes1. One class contains histone acetyltransferases (HATs), such as Gcn5 in the SAGA complex2, which acetylate nucleosomal histones. The second class contains ATPases, such as Swi2 in the Swi/Snf complex3, which provide the energy for nucleosome remodelling. In several promoters these two complexes cooperate but their functional linkage is unknown4,5,6,7,8. A protein module that is present in all nuclear HATs, the bromodomain, could provide such a link9. The recently reported in vitro binding of a HAT bromodomain with acetylated lysines within H3 and H4 amino-terminal peptides10 indicates that this interaction may constitute a targeting step for events that follow histone acetylation. Here we use a suitable promoter to show that bromodomain residues essential for acetyl-lysine binding are not required in vivo for Gcn5-mediated histone acetylation but are fundamental for the subsequent Swi2-dependent nucleosome remodelling and consequent transcriptional activation. We show that the Gcn5 bromodomain stabilizes the Swi/Snf complex on this promoter.

Irene Topalidou

Papers

The Gcn5 bromodomain co-ordinates nucleosome remodelling