Hampsey Laboratory

Michael Hampsey, PhD BA - 1976 - SUNY Geneseo PhD - 1982 - Purdue University Professor and Interim Chair Department of Biochemistry Robert Wood Johnson Medical School School of Public Health – Rm 285 683 Hoes Lane West Piscataway, NJ  08854-0009 Telephone: 732-235-5888 Facsimile:   732-235-5889 E-mail: michael.hampsey@umdnj.edu Department of Biochemistry Rutgers/UMDNJ Graduate Program

Research Fields

• Gene Expression 
• Chromatin 
• Yeast Genetics

Research Description

Our laboratory studies the regulation of gene expression in eukaryotic organisms. We are especially interested in transcription of protein-encoding genes by RNA polymerase II (Pol II).   The experimental organism used in most of our work is the yeast Saccharomyces cerevisiae , which enables us to use a powerful combination of classical genetics, molecular biology and modern biochemistry in our research.   Our current efforts are focused on two questions:   1) How is the transcription coupled to RNA processing? and 2) How do gene loops that juxtapose the 3'-end of the gene with the promoter affect the mechanism and regulation of gene expression?

1) Coupling of 3' end processing to Pol II transcription.   Nascent mRNA undergoes modifications that include 5' capping, splicing, 3' endonucleolytic cleavage and polyadenylation.   These processing events occur co-transcriptionally and involve recruitment and exchange of processing enzymes to the C-terminal domain (CTD) of the Rpb1 subunit of Pol II.   The CTD is phosphorylated and dephosphorylated at Ser2 and Ser5 during the transcription cycle.   We recently discovered that the Ssu72 protein is an integral component of the CPF 3' end processing complex and is a CTD Ser5-P phosphatase.   We are now focused on (i) determining how Ssu72-mediated Ser5-P dephosphorylation affects Pol II progression through the transcription cycle; (ii) how Ssu72 is regulated by the transcriptional machinery; and (iii) how Ssu72 is regulated by 3' end processing factors.   These questions are being addressed in collaboration with Professor Claire Moore ( Tufts Medical School ).  

2) Role of “gene loops” in transcription.   Although Ssu72 is a component of the CPF 3' end processing complex, we first identified this protein based on genetic and physical interactions with TFIIB, a transcription initiation factor.   As such, Ssu72 defined an unexpected link between the Pol II initiation and termination machineries.   This suggested to us that the ends of gene might physically interact to form gene loops.   Our recent studies revealed that gene loops are a general feature of Pol II transcription. Looping is dependent upon transcription and requires specific components of the transcription initiation and 3'-end processing complexes, including the Ssu72 CTD phosphatase. We are now working (i) to define the factors and mechanisms involved in loop formation; and (ii) to determine the functional significance of gene loops with respect to regulation of gene expression.

A remarkable feature of Pol II transcription and mRNA processing is the extent to which these two coupled processes – and the proteins that facilitate them – are conserved among eukaryotic organisms.   Accordingly, we are able to exploit the extensive arsenal of experimental approaches available in yeast with the results directly applicable to human biology and medicine.

Selected Publications:

ESTRELLA, L. A., S. KRISHNAMURTHY, C. R. TIMME and M. HAMPSEY (2008) The Rsp5 E3 ligase mediates turnover of low-affinity phosphate transporters in Saccharomyces cerevisiae. J. Biol. Chem. 283:5327-5334.

SINGH, B. N. and M. HAMPSEY (2007) A transcription-independent role for TFIIB in gene looping. Mol. Cell 27:806-816.

REYES-REYES, M. and M. HAMPSEY (2007) Role for the Ssu72 C-terminal domain phosphatase in RNA polymerase II transcription elongation. Mol. Cell. Biol. 27:926-936.

HAMPSEY, M. (2006) The RNA polymerase II initiation complex: looking for a place to start. Nat. Struct. Mol. Biol. 13 :564-566.

ANSARI, A. and M. HAMPSEY (2005) A role for the CPF 3'-end processing machinery in RNAP II-dependent gene looping. Genes & Dev. 19 :2969-2978.  

KRISHNAMURTHY, S., X. HE, M. REYES-REYES, C. MOORE AND M. HAMPSEY (2004) Ssu72 is a RNA polymerase II CTD phosphatase. Mol. Cell 14 :387-394.

CHEN, B.-S. and M. HAMPSEY (2004) Functional interaction between TFIIB and the Rpb2 subunit of RNA polymerase II: implications for the mechanism of transcription start site selection. Mol. Cell Biol. 24 :3983-3991.

HAMPSEY, M. and D. REINBERG (2003)  Tails of intrigue: phosphorylation of RNA polymerase II mediates histone methylation. Cell 113 :429-432. 

HE, X., A.U. KHAN, H. CHENG, D.L. PAPPAS, M. HAMPSEY and C.L. MOORE   (2003)  Functional interactions between the transcription and mRNA 3' end processing machineries mediated by Ssu72 and Sub1. Genes & Dev. 17 :1030-1042.

WOYCHIK, N.A. and M. HAMPSEY  (2002)  The RNA polymerase II machinery: structure illuminates function. Cell 108 :453-463.

Laboratory Personnel :

Adjunct Assistant Professor

• Krishnamurthy Shankarling, PhD

Postdoctoral Fellow:

• Badri Nath Singh, PhD

Graduate Students:

• Shivani Goel , MS
• Jesus Rosado, BS

Former Postdoctoral Fellows/Graduate Students/Research Technicians:

Athar Ansari, Ph.D., adjunct assistant professor

Jean-Philippe Lainé, Ph.D., postdoctoral fellow

Mariela Reyes-Reyes, Ph.D., 2006, graduate student

Luis A. Estrella, Ph.D., 2004, graduate student

Asad U. Khan, Ph.D., postdoctoral fellow

Bo-Shiun Chen, Ph.D., 2003, graduate student

Wei-Hua Wu, Ph.D., 2001, graduate student

M. Angeles Freire-Picos, Ph.D., postdoctoral fellow; visiting professor

Amy Tessmer Pappas, research techician

Donald L. Pappas, Jr., Ph.D., 2000, graduate student

Zu-Wen Sun, Ph.D., 1996, graduate student, postdoctoral fellow

Rhonda W. Berroteran, Ph.D., 1995, research tech., graduate student

Katy O'Mara, research technician

Dan E. Ware, M.S., M.D., 1991, graduate student

Jong G. Na, Ph.D., 1992, graduate student

Inés Pinto, Ph.D., 1992, graduate student

Former Undergraduate Students:

Sophia Sequeira, undergraduate student (Williams College)

Cindy R. Timme, B.S., undergraduate student (Rutgers)

Dianaliz Santiago, B.S., (Univ. Puerto Rico - Mayagüez)

Mark Neurohr-Pierpaoli, B.S., undergraduate student (Rutgers)

Jin Cho, B.S., undergraduate student (Rutgers)

Ashis Bhutani, B.S., undergraduate student (Rutgers)

Alexandra Terskiy, B.S., undergraduate student (Rutgers)

Francia Francis, B.S., undergraduate student (Rutgers)

Annette Seda, undergraduate student (Univ. Puerto Rico - Mayagüez)

Dimple Patel, B.S., undergraduate student (Rutgers)

Taly Garcia-Muñiz, B.S., undergraduate student (Rutgers)

Vimal Patel, B.S., undergraduate student (Rutgers)

Sonal Patel, B.S., undergraduate student (Rutgers)

Rajan Mitchell, B.S., undergraduate student (Rutgers)

Mary Mai, B.S., undergraduate student (Rutgers)

Jeffrey Beasley, high school student (Louisiana)