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A study published in Nature Chemical Biology presents the first chemical probe that can inhibit a certain complex of proteins that play a major role in repressing gene transcription, which is the first step in the process of reading DNA, the genetic blueprint for all structures in the cell, to make proteins.

Stephen Frye, PhD, is a UNC Lineberger member and Fred Eshelman Distinguished Professor in the UNC Eshelman School of Pharmacy.

Researchers have found a new cellular probe that they believe can be used to block the function of cellular proteins that help repress transcription, which is the process of turning DNA into the language used by the body for making proteins.

The study, published in the journal Nature Chemical Biology, reports on the first reported active chemical probe for any member of the chromodomain family of proteins that recognize, or “read,” methylated lysine. Specifically, the probe inhibits the CBX chromodomains that participate in Polycomb repressive complex 1 (PRC1), one of the major regulatory complexes involved in repression of gene transcription.

The PCR1 complex plays a major role in differentiation and development, said Lindsey I. James, PhD, research assistant professor in the UNC Eshelman School of Pharmacy. Importantly, the researchers have extremely well characterized the probe using structural biology and selectivity studies, as well as biochemically, James said.

” The chemical probe we developed will better assist us and others in investigating the oncogenic activities of these important proteins, and allow probe-enabled biological hypotheses to be tested, while also determining if PRC1 reader proteins are viable drug targets,” James said. “As methyl-lysine reader proteins are a less precedented class of epigenetic targets, we hope that this work will encourage additional efforts in targeting members of this important class of regulatory proteins.”

James and Stephen Frye, PhD, a UNC Lineberger member and Fred Eshelman Distinguished Professor in the UNC Eshelman School of Pharmacy, were corresponding authors of the study.

Read the study here.