Characterization of the novel nucleic acid binding function of bromodomains in the chromatin remodeler PBAF

Every cell in the human body contains a complete copy of the genome, DNA molecules that carry the heritable blueprint for life. However, the regulation of the genome is distinct between cells leading to the variety of cell-types necessary to build a human. This is accomplished in part through chromatin, which consists of the DNA molecules in complex with proteins known as histones. Chromatin, both packages the DNA into the cell as well as regulates it. The basic repeating subunit of chromatin is known as the nucleosome. The positioning of the nucleosomes regulates the genome and determines cell fate. Large protein complexes known as chromatin remodeling complexes, chemical modification of the histones and RNA molecules help to regulate the nucleosome positioning. The remodeling complexes move the histones around, whereas the modifications and RNA regulate the remodeling complexes.

PBAF (Polybromo-associated BRG1 or hBRM-associated factors) is one such remodeling complex is known to be regulated by modifications on the histones and RNA. The PBAF complex contains eight bromodomains, which are thought to be important for regulating its function. In the research described here, it was discovered that, in addition to binding to chemical modifications on the histones, four of these bromodomains can also bind to genomic DNA or RNA molecules. In addition, the interaction mechanisms of bromodomains with DNA and RNA were determined as well. Thus, this work sheds light on the function of these domains in regulating PBAF and the human genome.