Dr. Martens received his Ph.D. in 1999 with Chris Brandl at the University of Western Ontario, performed his postdoctoral studies with Fred Winston at Harvard University, and joined the Department in 2005.
Normal cell growth and development is dependent on a dynamic gene expression program where genes are turned on when they are needed and turned off when they are no longer required. Failure to maintain proper control of gene expression can lead to cell death or uncontrolled cell growth; two fates that often are at the root of many human diseases and cancers. Research in our lab focuses on understanding the molecular mechanisms that are involved in controlling gene expression in the budding yeast, Saccharomyces cerevisiae. Two important points make S. cerevisiae an excellent model organism to study gene regulation: 1) an outstanding array of genetic, genomic, and molecular tools are readily available (Figure 1) and 2) many gene regulatory mechanisms and proteins that are involved in these mechanisms are highly conserved in human cells.
Our understanding of the control of transcription initiation has been primarily based on studies that identified and characterized protein factors that play diverse roles in these processes. However, it is becoming increasingly clear that, in addition to these proteins, the transcription of non-protein-coding DNA (ncDNA) can have profound effects on the regulation of gene expression. Recent whole-genome expression studies revealed that transcription of ncDNA represents ~80 of the transcriptional output of eukaryotic organisms ranging from yeast and human. Our research is focused on understanding the impact of ncDNA transcription on the regulation of protein-coding gene expression.
In S. cerevisiae, we have uncovered a novel gene repression mechanism that involves transcription of ncDNA (Figure 2). What is unique about this mechanism is that the ncRNA product is not required for repression, rather it is the act of transcribing the ncDNA that represses the adjacent protein-coding gene by interfering with the binding of transcriptional activators. Using these studies as our foundation, we continue to investigate the impact of intergenic transcription on gene expression. Current research activities include:
- Identification and characterization of factors that are involved in repression by intergenic transcription
- Analysis of a possible role for intergenic transcription in modifying chromatin structure and/or histone modifications
- Identification and characterization of new cases of intergenic transcription and their impact on gene expression
Hainer SJ, Charsar BA, Cohen S, and Martens JA. (2012) Identification of mutant versions of the transcription elongation factor Spt16 that are defective for transcription-coupled nucleosome occupancy. G3: Genes, Genomes, Genetics. May;2:555-567.
Pruneski JA, Hainer SJ, Petrov KP, and Martens JA. (2011) The Paf1 Complex represses SER3 transcription in Saccharomyces cerevisiae by facilitating intergenic transcription-dependent nucleosome occupancy of the SER3 promoter. Euk Cell. Oct;10(10):1283-94.
Hainer SJ and Martens JA. (2011) Identification of histone mutants that are defective for transcription-coupled nucleosome occupancy. Mol Cell Biol. Sep;31(17):3557-68
Hainer SJ and Martens JA. (2011) Transcription of ncDNA: many roads lead to local gene regulation. Transcription. May;2(3):120-123.
Pruneski JA, and Martens JA. (2011) Transcription of intergenic DNA deposits nucleosomes on promoter to silence gene expression. Cell Cycle. Apr;10(7):1021-22.
Thebault P, Boutin G, Bhat W, Rufiange A, Martens J, and Nourani A. (2011) Transcription regulation by the noncoding RNA SRG1 requires Spt2-dependent chromatin deposition in the wake of RNA polymerase II. Mol Cell Biol. Mar;31(6):1288-300
Hainer SJ, Pruneski JA, Mitchell RD, Monteverde RM, and Martens, JA. (2011) Intergenic transcription causes repression by directing nucleosome assembly. Genes Dev. 25:29-40
Hartzog GA and Martens JA. (2009) ncRNA transcription makes its mark. EMBO J. 28:1679-1680
Martens JA, Wu PY, and Winston F. (2005) Regulation of an intergenic transcript controls adjacent gene transcription in Saccharomyces cerevisiae. Genes Dev. Nov;19(22):2695-704
Martens JA, Laprade L, and Winston F. (2004) Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene. Nature. Jun;429(6991):571-4
Martens JA and Winston F. (2003) Recent advances in understanding chromatin remodeling by Swi/Snf complexes. Curr. Opin. Genet. Dev. Apr;13(2):136-42.
Martens JA and Winston F. (2002) Evidence that Swi/Snf directly represses transcription in S. cerevisiae. Genes Dev. Sep;16(17):2231-6