PT  - JOURNAL ARTICLE
AU  - Sebastian Scheer
AU  - Suzanne Ackloo
AU  - Tiago S. Medina
AU  - Matthieu Schapira
AU  - Fengling Li
AU  - Jennifer A. Ward
AU  - Andrew M. Lewis
AU  - Jeffrey P. Northrop
AU  - Paul L. Richardson
AU  - H. Ümit Kaniskan
AU  - Yudao Shen
AU  - Jing Liu
AU  - David Smil
AU  - Minkui Luo
AU  - Jian Jin
AU  - Dalia Barsyte-Lovejoy
AU  - Kilian V. M. Huber
AU  - Daniel D. De Carvalho
AU  - Masoud Vedadi
AU  - Colby Zaph
AU  - Peter J. Brown
AU  - Cheryl H. Arrowsmith
TI  - A Chemical Biology Toolbox for the Study of Protein Methyltransferases and Epigenetic Signaling
AID  - 10.1101/260638
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 260638
4099  - http://biorxiv.org/content/early/2018/02/07/260638.short
4100  - http://biorxiv.org/content/early/2018/02/07/260638.full
AB  - 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.