A Chemical Biology Toolbox for the Study of Protein Methyltransferases and Epigenetic Signaling

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Author(s)

Author Name

Sebastian Scheer

Published 1 Project

Biochemistry

Suzanne Ackloo

Published 3 Projects

Biochemistry Cell Biology

Tiago S. Medina

Published 1 Project

Biochemistry

Matthieu Schapira

Associate Professor, University of Toronto

Published 8 Projects

Bioinformatics Biochemistry Pharmacology And Toxicology Cell Biology

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Fengling Li

Jennifer A. Ward

Published 1 Project

Biochemistry

Andrew M. Lewis

Published 1 Project

Biochemistry

Jeffrey P Northrop

Published 1 Project

Biochemistry

Paul L Richardson

Published 1 Project

Biochemistry

H. Ümit Kaniskan

Published 1 Project

Biochemistry

Yudao Shen

Published 2 Projects

Biochemistry

Jing Liu

Published 2 Projects

Biochemistry

David Smil

Minkui Luo

Published 2 Projects

Biochemistry

Jian Jin

Published 3 Projects

Biochemistry

Dalia Barsyte

Kilian V.M. Huber

Published 1 Project

Biochemistry

Daniel D. De Carvalho

Published 1 Project

Biochemistry

Masoud Vedadi

Colby Zaph

Published 1 Project

Biochemistry

Peter J Brown

Cheryl H Arrowsmith

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Protein methyltransferases (PMTs) comprise a major class of epigenetic regulatory enzymes with therapeutic relevance. Here we present a collection of chemical probes and associated reagents and data to elucidate the function of human and murine PMTs in cellular studies. Our collection provides inhibitors and antagonists that together modulate most of the key regulatory methylation marks on histones H3 and H4, providing an important resource for modulating cellular epigenomes. We describe a comprehensive and comparative characterization of the probe collection with respect to their potency, selectivity, and mode of inhibition. We demonstrate the utility of this collection in CD4+ T cell differentiation assays revealing the remarkable potential of individual probes to alter multiple T cell subpopulations with important implications for T cell-mediated processes such as inflammation and immuno-oncology. In particular, we demonstrate a role for DOT1L in limiting Th1 cell differentiation and maintaining lineage integrity.

Biochemistry
Biochemistry 9 Projects