Characterization of the novel DNA binding activity of the BRG1 AT-hook-bromodomain

Genomic DNA is packaged inside the nucleus of cells in the form of repeating units called nucleosomes. The DNA organized in nucleosomes is called chromatin. Each cell in the human body contains virtually the same DNA sequence. However, cells have different proteins expressed by specific genes depending on the tissue type. This differential pattern of gene expression is aided in part by a process of DNA compaction and decompaction. Here, nucleosomes play a crucial role in compacting stretches of DNA and thus regulating DNA-templated processes such as gene expression. The BRG1/BRM associated factor (BAF) complex is a multiprotein complex with a central ATPase subunit (BRG1) in charge of transforming the energy of ATP into mechanical motion. BAF is involved in decompacting/compacting chromatin and facilitating or preventing access to the underlying DNA.

At the end of the BRG1 subunit there is a domain known as bromodomain with an adjacent unstructured region at its N-terminus known as the AT-hook. This composite region is denoted as the ATBD. My work revealed a DNA binding property previously uncharacterized for the bromodomain portion of the ATBD. This DNA binding ability of the bromodomain exhibits moderate specificity for a particular sequence in DNA. This work also revealed in detail the molecular contacts between the ATBD and DNA. Together, these results paved the way to investigate the regulatory functions of the ATBD in the context of the BRG1 subunit and in the context of BAF.