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Endogenous Mediator complexes with cell type specific functions

The Mediator complex is an essential regulator of RNAP II function, required for basal and activator-induced transcription of nearly all protein coding genes. About half of the 30 subunits that compose the Mediator complex are targeted by transcription factors to convey an array of biological inputs to the RNAP II enzyme. Although Mediator composition appears to be monolithic across most human cell types, some subunits are not expressed in specific differentiated cell types and cancer cell lines. The absence of crucial Mediator subunits has the potential to alter global gene expression, cell signaling and proliferation. We know very little about whether endogenous Mediator complexes lacking specific subunits exist in human cells. I am using a variety of in vitro and cell-based methods to explore this question, and to address the function of Mediator complexes with altered subunit composition, and how they may contribute to disease.  

Publications

Richter WF, Nayak S, Iwasa J, Taatjes DJ. The Mediator complex is a master regulator of RNA polymerase II transcription. Nat Rev Mol Cell Biol 2022, 23: 732 - 749.

Richter WF, Shah RN, Ruthenburg AJ. Non-canonical H3K79me2-dependent pathways promote the survival of MLL-rearranged leukemia. eLife 2021, 10:e64960. 

Grzybowski AT, Shah RN, Richter WF, Ruthenburg AJ. Native internally calibrated chromatin immunoprecipitation for quantitative studies of histone post-translational modifications. Nat Protoc 2019, 14:3275-3302. 

Beshiri ML, Holmes KB, Richter WF, Hess S, Islam ABMMK and Benevolenskaya EV. Coordinated repression of cell cycle genes by KDM5A andE2F4 during differentiation. Proc Natl Acad Sci USA 2012, 109:18499-504. 

Islam ABMMK, Richter WF, Jakobs L, Lopez-Bigas N and Benevolenskaya EV. 2011. Coregulation of histone-modifying enzymes in cancer. PLoS One 2011 8:e24023. 

Islam AB, Richter WF, Lopez-Bigas N, Benevolenskaya EV. Selective targeting of histone methylation. Cell Cycle 2011 10:413-24. 

Beshiri ML, Islam A, DeWaal DC, Richter WF, Love J, Lopez-Bigas N, Benevolenskaya EV. Genome-wide analysis using ChIP to identify isoform-specific gene targets. J Vis Exp. 2010 Jul 7;(41) 

Wang Q, Anzick S, Richter WF, Meltzer P, Simons SS Jr. Modulation of transcriptional sensitivity of mineralocorticoid and estrogen receptors. J Steroid Biochem Mol Biol 2004 91:197-210.