Biochemistry and Molecular Biology
Penn State Science
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Joseph Reese

Joseph Reese

Main Content

  • Professor of Biochemistry and Molecular Biology
463A North Frear Laboratory
University Park, PA 16802
Phone: (814) 865-1976

Research Interests

Chromatin structure and gene expression, DNA damage resistance pathways

Graduate Programs


Research Summary

Stress induced gene expression and UV resistance pathways
Cancer results from of an accumulation of genetic and cellular damage and the ensuing uncontrolled cell proliferation. Eukaryotic cells respond to these challenges by activating DNA damage sensing, signaling and repair pathways that are stimulated by damage to DNA and other stresses. Activation of these pathways cause the execution of cell cycle delays, referred to as checkpoints, and the expression of DNA repair genes. Alterations in these functions are known to predispose people to cancer and other diseases. Our laboratory uses a combination of biochemistry, genetics, genomics and molecular biology to study the mechanisms controlling stress-induced changes in gene expression in eukaryotes. The two main focus areas of the lab are the role of transcription and mRNA decay factors in regulating the DNA damage response and the control of transcription elongation by protein complexes and chromatin.

Regulation of mRNAs from birth to death during stress responses
Gene expression is controlled at multiple levels, requiring highly regulated and integrated events including chromatin remodeling, initiation, elongation, processing, transport and ultimately the destruction of mRNA. Determining how these events are coordinated is essential to understanding gene expression mechanisms. Our research exploits the powerful genetic systems of budding yeast and Drosophila melanogaster to examine the function of a complex proposed to perform multiple steps in gene regulation: the Ccr4-Not complex.  The Ccr4-Not complex is highly conserved across the eukaryotic kingdom. Initially purposed to be a nuclear transcription regulatory complex in yeast, it has since been identified as the major mRNA deadenylase in the cytoplasm and implicated in protein destruction and micro RNA (miRNA) processing.  Mutations in subunits of this complex cause altered DNA damage checkpoint functions, impaired cell cycle progression and sensitivity to stress. The human orthologues of these proteins are putative oncogenes and are implicated in regulating hepatitis C virus replication in human cells; thus, understanding the function of this complex is directly relevant to human disease. The goals of our project studying Ccr4-Not are to (1) uncover how multiple steps in gene expression are coordinated and regulated; (2) define the functions of a highly conserved eukaryotic transcription factor complex implicated in human disease; (3) identifying how specific mRNAs are marked for post-transcriptional control during transcription.

Control of RNA Polymerase II elongation and regulation of chromatin structure during elongation
Transcription of a gene requires the movement of RNA polymerase II (RNAPII) across many thousands of bases in the genome. Throughout the elongation process, RNAPII acquires and releases up to 29 different multisubunit complexes to allow it to transverse a gene. Elongation factors assist RNAPII in transcribing through chromatin and transcription blocks, and successful completion of the gene requires the coordinated action of elongation factors and the remodeling of chromatin ahead of RNAPII.  We are analyzing the recruitment and actions of elongation factors during RNAPII elongation in vitro and in vivo. Using highly purified factors and reconstitution biochemistry, we can monitor the assembly and disassembly of elongation complexes to gain mechanistic insights into how elongation factors promote transcription elongation.  Furthermore, we can exploit the highly tractable genetic system of yeast to monitor elongation in vivo and to interrogate the role of the structure of the nucleosome in regulating elongation.

Reese figure 1

Figure 1. Gene expression is regulated at multiple levels in the nucleus and cytoplasm.



Reese figure 2

Figure 2. Ccr4-Not functions in the nucleus and cytoplasm to control the synthesis and destruction of mRNAs during the stress response

Selected Publications

  • Crickard, J.B. , Lee, J, Lee, T-H and Reese, J.C.  (2017). The elongation factor Spt4/5 regulates RNA polymerase II transcription through the nucleosome. Nucleic Acids Research, 45:6362-6374.
  • Crickard, J.B., J. Fu and J.C. Reese. (2016). Biochemical Analysis of Yeast Suppressor of Ty 4/5 (Spt4/5) Reveals the Importance of Nucleic Acid Interactions in the Prevention of RNA Polymerase II Arrest J. Biol. Chemistry 291, 9853-9870.
  • Dutta, A, V Babbarwal, J Fu, D Brunke-Reese, DM Libert, J Willis and JC Reese (2015) Ccr4-Not and TFIIS function cooperatively to rescue arrested RNA polymerase II. Mol. Cell Biol, 35:1915-1925.
  • Babbarwal, V., J. Fu and J.C. Reese (2014). The Rpb4/7 module of RNA polymerase II is required for Carbon Catabolite Repressor Protein 4-Negative on TATA (Ccr4-Not) complex to promote elongation . J. Biol. Chem., 289:33125-30.
  • Collart, M. and J.C. Reese (2014)  Gene expression as a circular process: cross-talk between transcription and mRNA degradation in eukaryotes. RNA Biology 4, 320-323.
  • Zheng, S., J.B. Crickard, A. Srikanth and J.C. Reese. (2014). A highly conserved domain within H2B is required for FACT to remove H2A/2B dimers from chromatin. Molecular and Cellular Biology. 34, 303-314.
  • Reese, J.C. (2013) Control of elongation by the Ccr4-Not complex. BBA-Gene Regulatory Mechanism. 1829, 127-133.
  • Miller, J.E. and J.C. Reese (2012). Ccr4-Not: the control freak of the cell. Critical Reviews in Biochemistry and Molecular Biology. 47, 315-333.
  • Dutta, A., S. Zheng, D. Jain, C.E. Cameron and J.C. Reese (2011). Intermolecular interactions within the abundant DEAD-box protein Dhh1 modulate its activity in vivo. J. Biol. Chem., 286, 27454-27470.

  • Kruk, J.A., A. Dutta, J. Fu, D.S. Gilmour and J.C. Reese (2011). The multifunctional Ccr4-Not complex directly promotes transcription elongation. Genes and Development, 25, 581-93.

  • Zheng, S., J. Wyrick and J.C. Reese (2010). Novel trans-tail regulation of H2B ubiquitylation and H3K4 methylation by the N-terminus of Histone H2A. Molecular and Cellular Biology 30, 3635-3645.
  • Krajewski, W.A. and J.C. Reese (2010). SET domains of histone methyltransferases recognize ISWI-remodeled nucleosomal species. Molecular and Cellular Biology 30, 552-564.
  • Psathas, J.N., S. Zheng, S. Tan and J. C. Reese (2009). Set2-dependent K36 methylation is regulated by novel intra-tail interactions within H3. Molecular and Cellular Biology 29, 6413-26.
  • Trazzi, S., G. Perini, R. Bernardoni, M. Zoli, J.C. Reese, A. Musacchio, and G.D.Valle (2009). The C-Terminal Domain of CENP-C Displays Multiple and Critical Functions for Mammalian Centromere Formation. PLoS ONE 4, e5832.
  • Tomar, R.S., J.N. Psathas, H. Zhang, Z. Zhang, and J.C. Reese (2009). A novel mechanism of antagonism between chromatin remodeling complexes in vivo. Mol. Cell. Biol. 29, 3255-3265.