Greehey CCRI Seminar Series, Fall ’23: Peter W Lewis, PhD, Univ of Wisconsin

Research Description

Our research seeks to define the biochemical mechanisms involved in the establishment and maintenance of silent chromatin, also known as heterochromatin. Our experimental approaches span the spectrum from highly purified biochemical assays to proteomic and genomic analyses and genetic screens.

Covalent modifications to DNA and histone proteins allow chromatin to act as a dynamic information hub that integrates diverse biochemical stimuli to regulate genomic DNA access for transcription. To preserve cell identity, lineage-specific gene expression must be maintained, and failure to silence genes from other lineages has the potential to cause developmental defects or promote tumorigenesis.

The Polycomb Repressive Complex 2 (PRC2) is one component of the two main Polycomb group protein complexes that function in collaborative crosstalk with K27 methylation on histone H3 (H3K27me3) to initiate and maintain transcriptional silencing. Misregulation of PRC2 and H3K27me3 can cause developmental defects and specific types of cancer. We seek to define the factors that impact PRC2 recruitment and activity by using a combination of biochemical and genomic approaches.

Heterochromatin containing H3K9me3 and methylated CpG nucleotides plays an important role in maintaining genome integrity by silencing transposable elements.  We found that H3K9me3, the histone variant H3.3 and its deposition factor ATRX-DAXX, and the Human Silencing Hub (HuSH) complex function together to silence retrotransposable elements in mammals. Our research seeks to define the pathways and factors involved in establishing heterochromatin at transposons and other highly repetitive genomic sequences.

Learn more about Dr. Lewis.