Dr. Michael Carey’s research focuses on the study of biochemical mechanisms of gene activation and silencing. In 1990, his lab established biochemical systems for the study of gene regulation based on a model transcriptional activator termed GAL4-VP16. Using that system, he established a mechanism by which genes are controlled synergistically by upstream activators, with synergy a key principle in gene regulation and the underlining of combinatorial control of gene transcription. Over the course of the decade, Carey's lab further identified that synergy is first manifested during assembly of transcription preinitiation complexes (PICs), and that the assembly of a co-activator complex (termed DAMed) is the key step influenced by activators.
Carey’s current research is focused on the biochemistry of transcription on chromatin templates. His lab recently showed how the protein p300 coordinates chromatin modification with assembly of the DAMed complex and then the PIC. Carey also demonstrated how the proteins HP1 and PRC1 silence transcription by selectively affecting key components of the DAMed complex. Most recently, Carey’s lab recreated the effects of histone methylation on gene activation and silencing in vitro, and applied gene regulation principles to co-develop transcription-based imaging systems for cancer.
Selected Cancer-Related Publications:
Chen XF, Lehmann L, Lin JJ, Vashisht A, Schmidt R, Ferrari R, Huang C, McKee R, Mosley A, Plath K, Kurdistani SK, Wohlschlegel J, Carey M. Mediator and SAGA have distinct roles in Pol II preinitiation complex assembly and function. Cell Rep. 2012 Nov 29;2(5):1061-7. doi: 10.1016/j.celrep.2012.10.019. Epub 2012 Nov 21.
Kitada T, Kuryan BG, Tran NN, Song C, Xue Y, Carey M, Grunstein M. Mechanism for epigenetic variegation of gene expression at yeast telomeric heterochromatin. Genes Dev. 2012 Nov 1;26(21):2443-55. doi: 10.1101/gad.201095.112.
Kuryan BG, Kim J, Tran NN, Lombardo SR, Venkatesh S, Workman JL, Carey M. Histone density is maintained during transcription mediated by the chromatin remodeler RSC and histone chaperone NAP1 in vitro. Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):1931-6. doi: 10.1073/pnas.1109994109. Epub 2012 Jan 23.
Chen XF, Kuryan B, Kitada T, Tran N, Li JY, Kurdistani S, Grunstein M, Li B, Carey M. The Rpd3 core complex is a chromatin stabilization module. Curr Biol. 2012 Jan 10;22(1):56-63. doi: 10.1016/j.cub.2011.11.042. Epub 2011 Dec 15.
Lin JJ, Lehmann LW, Bonora G, Sridharan R, Vashisht AA, Tran N, Plath K, Wohlschlegel JA, Carey M. Mediator coordinates PIC assembly with recruitment of CHD1. Genes Dev. 2011 Oct 15;25(20):2198-209. doi: 10.1101/gad.17554711. Epub 2011 Oct 6.