Research interests in the Bowman lab

Chromatin remodelers are multi-domain enzymes that reorganize the structure and placement of nucleosomes throughout the genome. Remodelers can be classified into distinct families that appear to specialize in particular tasks: disrupting nucleosomal wrapping and evicting histone cores, replacing histone proteins with specialized variants, repositioning nucleosomes into evenly-spaced arrays, and catalyzing nucleosome assembly. In the Bowman lab, we are focused on the Chd1 chromatin remodeler, which has been shown to both assemble and evenly space nucleosomes (Lusser et al., 2005; Pointner et al., 2012 ; Ocampo et al., 2016). Unlike most other remodelers, Chd1 is monomeric and therefore provides an ideal model system for discovering how remodelers work. Chd1 was named for three recognizable domains: a pair of N-terminal chromodomains, a central helicase-like ATPase motor, and a C-terminal DNA-binding domain (Delmas et al., 1993).

histone swivel model

We are studying the architecture and organization of Chd1 to understand how remodeler domains communicate and influence each other, and thus how each domain contributes to the remodeling reaction. Our crystal structure of the chromo-ATPase portion of S. cerevisiae Chd1 revealed that the chromodomains can pack against a DNA-binding surface on the ATPase motor, providing the first example of how a remodeler ATPase motor can be auto-regulated (Hauk et al., 2010). We also showed that the DNA-binding domain was essential for directional sliding (McKnight et al., 2011), even though this domain binds DNA in a sequence-nonspecific manner (Sharma et al., 2011). Using site-specific cross-linking, we recently discovered a novel organization of remodeler domains on the nucleosome (Nodelman et al., 2017). This structural data has provided novel insight into how remodeler domains may work together. We are currently focused on three core questions regarding the mechanisms of Chd1 action and regulation:

     1. What role do the chromodomains play in the remodeling reaction?

     2. How does the Chd1 DNA-binding domain sense DNA outside the nucleosome core?

     3. How does the Chd1 ATPase motor shift DNA past the histone core?