Promoter targeting of chromatin-modifying complexes

The action of multi-subunit complexes that are able to overcome the repress ive effects of chromatin is an important step in the regulation of eukaryot ic gene expression. Identification of complexes that modify the structure o f chromatin to help factors access the underlying DNA has enhanced our unde rstanding of how some genes are controlled. Histone acetyltransferases (HAT s) and histone deacetylases (HDACs) represent one group of complexes that r egulate the level of acetylation on the N-terminal tails of core histone pr oteins. The SWI/SNF complex is the prototype of a second group of complexes , which use the energy of ATP-hydrolysis to alter histone-DNA contacts, lea ding to changes in chromatin conformation. Genetic studies in yeast have re vealed that some of these multi-subunit complexes interact in vivo to contr ol transcription of a subset of genes. It has become apparent that some gen e promoters require modifications by both types of complexes. An important question regarding these two types of complexes is how they are recruited t o the promoters of genes that are dependent on their activity for their exp ression. This review will tie together many studies on promoter recruitment of both HATs and SWI/SNF. Emphasis will be placed on recent data that demo nstrates functional interplay between these two types of chromatin-remodeli ng activities. In addition, this review summarizes recent data demonstratin g the ability of repressors and corepressors to recruit histone deacetylase complexes. Interestingly, many subunits of chromatin-modifying complexes i n humans have been implicated in the development of cancer. Thus, studying how these complexes work can help us better understand human diseases.