HMG Architectural Proteins: Understanding Sequence-Independent DNA Binding and Genome Accessibility (2011)

Undergraduates: Timothy Palpant, Colin Lickwar

Faculty Advisor: Jason Lieb
Department: Biology

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In order to appropriately respond to developmental and environmental signals, cells have evolved complex methods to regulate gene expression. In eukaryotic cells, chromatin acts as a fundamental mechanism of transcriptional regulation, and understanding the factors that establish chromatin structure in vivo is an ongoing challenge. The second most abundant component of chromatin is the HMG family of architectural proteins, yet relatively little is known about HMG localization and function. In order to identify the factors directing HMG binding, we mapped the in vivo binding sites of all seven HMG proteins in S. cerevisiae by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). We find extensive co-localization with repressor-activator protein (Rap1), a master transcriptional regulator. Furthermore, nucleosome positioning is altered upon deletion of the HMG proteins Nhp6A and Nhp6B, and sites of Nhp6A binding have unusually high histone turnover. Taken together, these results suggest that HMG proteins may disrupt chromatin structure to facilitate transcription. We are currently testing this hypothesis by correlating changes in HMG localization and chromatin structure after transcriptional reprogramming.