Karen Arndt

  • Professor
  • Transcriptional control

Contact

Office: (412) 624-6963
Lab: (412) 624-6963
A316 Langley Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

Figure 1.  The multifunctional Paf1 complex associates with RNA pol II, promotes histone modifications coupled to active transcription, interacts with other transcription and chromatin factors, and regulates RNA 3’-end formation.

A critical question to ask, particularly in this genomic era, is how organisms interpret the vast amounts of information encoded in their genomes. The Arndt lab studies the first step in gene expression, the synthesis of mRNA by RNA polymerase II, with a focus on the mechanisms that regulate transcription in the chromatin environment of a eukaryotic cell.  The fundamental importance of understanding transcriptional regulation is evident from the large number of human developmental defects and diseases, including cancer and AIDS, that arise when cellular transcription factors are altered by mutation or commandeered by viral proteins.

The transcription cycle can be divided into three steps: (1) promoter recognition and initiation of RNA synthesis; (2) elongation of the growing RNA chain; and (3) termination.  Our current studies focus on the elongation and termination steps in the cycle.  In our research, we exploit a vast array of genetic, biochemical, and genomic tools uniquely available in the model eukaryote, Saccharomyces cerevisiae.  This simple yeast is an excellent model system for our studies because the proteins and mechanisms that regulate transcription have been highly conserved from yeast to man.

Figure 2.  High resolution DNA microarray technology can be used to identify transcriptional patterns in different yeast strains.

During transcription elongation, RNA polymerase II encounters obstacles, notably nucleosomes, which block its path.  Eukaryotes express proteins that facilitate or impede polymerase movement by altering the chromatin template.  One of these proteins is the conserved Paf1 complex. The Paf1 complex associates with RNA polymerase II on the coding regions of transcribed genes, interacts with other highly conserved elongation factors, couples histone modification to transcription elongation, and controls the efficiency of transcription termination.  Thus, the Paf1 complex is a multifunctional regulator of gene expression that lies at the intersection between transcription elongation and chromatin modification.  Current projects in the lab are focused on:

  • The mechanisms by which the Paf1 complex regulates transcription elongation and events coupled to this process, especially RNA 3' end formation
  • The genes that are regulated by the Paf1 complex and how the Paf1 complex is recruited to these genes
  • The mechanisms by which the Rtf1 subunit of the complex controls histone modifications
  • The functions of the Cdc73 subunit of the Paf1 complex, a protein with tumor suppression activity in human cells
  • The cellular factors, including a novel ubiquitin protein-ligase, that protect the cell against the consequences of deregulated transcription
E-mail Lab

Van Oss, S.B., Shirra, M. K., Bataille, A. R.,

Van Oss, S.B., Shirra, M. K., Bataille, A. R., Wier, A. D., Yen, K., Vinayachandran, V., Byeon, I.-J. L., Héroux, A., Cucinotta, C. E., Jeon, J., Kim, J., VanDemark, A. P., Pugh, B. F., and Arndt, K. M. (2016) The histone modification domain of Paf1 complex subunit Rtf1 directly stimulates H2B ubiquitylation through an interaction with Rad6.  Molecular Cell 64:815-825

Cucinotta, C.E. and Arndt, K.M. (2016) SnapShot

Cucinotta, C.E. and Arndt, K.M. (2016) SnapShot:  Transcription Elongation.  Cell 166: 1058

Raupach, E.A., Martens, J.A., and Arndt, K.M. (

Raupach, E.A., Martens, J.A., and Arndt, K.M. (2016) Evidence for regulation of ECM3 expression by intergenic transcription and methylation of histone H3 lysine 4 in Saccharomyces cerevisiae.  G3: Genes, Genomes, Genetics 6: 2971-2981.

Cucinotta, C. E., Young, A. N., Klucevsek, K. M

Cucinotta, C. E., Young, A. N., Klucevsek, K. M., and Arndt, K. M. (2015) The nucleosome acidic patch regulates the H2B K123 monoubiquitylation cascade and transcription elongation in Saccharomyces cerevisiae.  PLOS Genetics DOI:10.1371/journal.pgen.1005420.

Arndt, K.M. and Reines, D. (2015) Termination o

Arndt, K.M. and Reines, D. (2015) Termination of Transcription of Short Noncoding RNAs by RNA Polymerase II. Annu. Rev. Biochem., 84:22.1–22.24

Wier, A.D., Mayekar, M.K., Heroux, A., Arndt, K

Wier, A.D., Mayekar, M.K., Heroux, A., Arndt, K.M., VanDemark, A.P. (2013) The structural basis for Spt5-mediated recruitment of the Paf1 complex to chromatin. Proc. Natl. Acad. Sci. USA 110:17290-17295

Mayekar, M. K., Gardner, R. G., and Arndt K. M.

Mayekar, M. K., Gardner, R. G., and Arndt K. M. (2013) The recruitment of the Saccharomyces cerevisiae Paf1 complex to active genes requires a domain of Rtf1 that directly interacts with the Spt4-Spt5 complex.  Mol. Cell Biol., 33: 3259-3273

Tomson, B.N., Crisucci, E.M., Heisler, L.E., Ge

Tomson, B.N., Crisucci, E.M., Heisler, L.E., Gebbia, M., Nislow, C. and Arndt, K.M. (2013) Effects of the Paf1 complex and histone modifications on snoRNA 3'-end formation reveal broad and locus-specific regulation. Mol. Cell. Biol., 33:170-182

Tomson, B.N. and Arndt, K.M. (2013) The many ro

Tomson, B.N. and Arndt, K.M. (2013) The many roles of the conserved eukaryotic Paf1 complex in regulating transcription, histone modifications, and disease states. Biochim. Biophys. Acta 1829:116-126

Piro, A. S., Mayekar, M. K., Warner, M. H., Dav

Piro, A. S., Mayekar, M. K., Warner, M. H., Davis, C. P., and K. M. Arndt (2012) Small region of Rtf1 protein can substitute for complete Paf1 complex in facilitating global histone H2B ubiquitylation in yeast.  Proc. Natl. Acad. Sci. USA 109:10837-10842

Klucevsek, K.M., Braun, M.A., and K.M. Arndt (2

Klucevsek, K.M., Braun, M.A., and K.M. Arndt (2012) The Paf1 complex subunit Rtf1 buffers cells against the toxic effects of [PSI+] and defects in Rkr1-dependent protein quality control in Saccharomyces cerevisiae.  Genetics 191: 1107-1118

Amrich, C.G., Davis, C.P., Rogal, W.P., Shirra,

Amrich, C.G., Davis, C.P., Rogal, W.P., Shirra, M.K., Heroux, A., Gardner, R.G., Arndt, K.M. and VanDemark, A.P. (2012) The Cdc73 subunit of the Paf1 complex contains a C-terminal Ras-like domain that promotes association of the Paf1 complex with chromatin. J. Biol. Chem., 287:10863-10875.

Crisucci, E.M. and Arndt, K.M. (2012) Paf1 rest

Crisucci, E.M. and Arndt, K.M. (2012) Paf1 restricts Gcn4 occupancy and antisense transcription at the ARG1 promoter.  Mol. Cell Biol. 32:1150-1163

The roles of the Paf1 complex and associated histone modifications in regulating gene expression

Crisucci, E.M. and K.M. Arndt (2011) The roles of the Paf1 complex and associated histone modifications in regulating gene expression.  Genetics Research International 2011:doi:10.4061/2011/707641

Crisucci, E.M. and K.M. Arndt (2011) The Paf1 c

Crisucci, E.M. and K.M. Arndt (2011) The Paf1 complex represses ARG1 transcription in Saccharomyces cerevisiae by promoting histone modifications. Euk. Cell 10:712-723

Tomson, B.N., C.P. Davis, M.H. Warner, and K.M. Arndt (2011) Identification of a role for histone

Tomson, B.N., C.P. Davis, M.H. Warner, and K.M. Arndt (2011) Identification of a role for histone H2B ubiquitylation in non-coding RNA 3'-end formation through mutational analysis of Rtf1 in S. cerevisiae. Genetics 188: 273-289

Shirra, M.K., R.R. McCartney, C. Zhang, K.M. Shokat, M.C. Schmidt, and K.M. Arndt (2008) A chemic

Shirra, M.K., R.R. McCartney, C. Zhang, K.M. Shokat, M.C. Schmidt, and K.M. Arndt (2008) A chemical genomics study identifies Snf1 as a repressor of GCN4 translation. J. Biol. Chem. 283:35889-35898

Rubenstein, E.M., R.R. McCartney, C. Zhang, K.M. Shokat, M.K. Shirra, K.M. Arndt, and M.C. Schmid

Rubenstein, E.M., R.R. McCartney, C. Zhang, K.M. Shokat, M.K. Shirra, K.M. Arndt, and M.C. Schmidt (2008) Access denied: Snf1 activation loop phosphorylation is controlled by availability of the phosphorylated threonine 210 to the PP1 phosphatase. J. Biol. Chem. 283:222-230

Arndt, K.M. (2007) Molecular biology: genome under surveillance. Nature 450

Arndt, K.M. (2007) Molecular biology: genome under surveillance. Nature 450:959-960

Chu, Y., R. Simic, M.H. Warner, K.M. Arndt, and G. Prelich (2007) Regulation of histone modificat

Chu, Y., R. Simic, M.H. Warner, K.M. Arndt, and G. Prelich (2007) Regulation of histone modification and cryptic transcription by the Bur1 and Paf1 complexes. EMBO J. 26:4646-4656

Warner, M.H., K.L. Roinick, and K.M. Arndt (2007) Rtf1 is a multifunctional component of the Paf1

Warner, M.H., K.L. Roinick, and K.M. Arndt (2007) Rtf1 is a multifunctional component of the Paf1 complex that regulates gene expression by directing cotranscriptional histone modification. Mol. Cell Biol. 27:6103-6115

Braun, M.A., P.J. Costa, E.M. Crisucci, and K.M. Arndt (2007) Identification of Rkr1, a nuclear R

Braun, M.A., P.J. Costa, E.M. Crisucci, and K.M. Arndt (2007) Identification of Rkr1, a nuclear RING domain protein with functional connections to chromatin modification in Saccharomyces cerevisiae. Mol. Cell. Biol. 27:2800-2811

Sheldon, K.E., D.M. Mauger, and K.M. Arndt (2005) A requirement for the Saccharomyces cerevis

Sheldon, K.E., D.M. Mauger, and K.M. Arndt (2005) A requirement for the Saccharomyces cerevisiae Paf1 Complex in snoRNA 3' end formation. Mol. Cell 20:225-236

Arndt, K., and F. Winston (2005) An unexpected role for ubiquitylation of a transcriptional activ

Arndt, K., and F. Winston (2005) An unexpected role for ubiquitylation of a transcriptional activator. Cell 120:733-734 

Shirra, M.K., S.E. Rogers, D.E. Alexander, and K.M. Arndt (2005) The Snf1 protein kinase and Sit4

Shirra, M.K., S.E. Rogers, D.E. Alexander, and K.M. Arndt (2005) The Snf1 protein kinase and Sit4 protein phosphatase have opposing functions in regulating TBP association with the Saccharomyces cerevisiae INO1 promoter. Genetics 169:1957-1972

Arndt, K.M., and C.M. Kane (2003) Running with RNA polymerase: eukaryotic transcript elongation.

Arndt, K.M., and C.M. Kane (2003) Running with RNA polymerase: eukaryotic transcript elongation. Trends Genet. 19:543-550

Simic, R., D.L. Lindstron, H.G. Tran, K.L. Roinick, P.J. Costa, A.D. Johnson, G.A. Hartzog, and K

Simic, R., D.L. Lindstron, H.G. Tran, K.L. Roinick, P.J. Costa, A.D. Johnson, G.A. Hartzog, and K.M. Arndt (2003) Chromatin remodeling protein Chd1 interacts with transcription elongation factors and localizes to transcribed genes. EMBO J. 22:1846-4856

Spencer, J.V., and K.M. Arndt (2002) A TATA binding protein mutant with increased affinity for DN

Spencer, J.V., and K.M. Arndt (2002) A TATA binding protein mutant with increased affinity for DNA directs transcription from a reversed TATA sequence in vivo. Mol. Cell. Biol. 22:8744-8755

Squazzo, S.L., P.J. Costa, D. Lindstrom, K.E. Kumer, R. Simic, J.L. Jennings, A.K. Link, K.M. Arn

Squazzo, S.L., P.J. Costa, D. Lindstrom, K.E. Kumer, R. Simic, J.L. Jennings, A.K. Link, K.M. Arndt, and G. Hartzog (2002) The Paf1 complex physically and functionally associates with transcription elongation factors in vivo. EMBO J. 21:1764-1774
Dr. Arndt received her Ph.D. in 1988 with Michael Chamberlin at the University of California at Berkeley, performed her postdoctoral studies with Fred Winston at Harvard Medical School, and joined the Department in 1994.