Marc Gartenberg Professor UMDNJ-RWJMS Department of Pharmacology RWJMS Research Building Room 284 683 Hoes Lane West Piscataway. NJ 08854 (732) 235-5800 gartenbe@umdnj.edu

Sister chromatid cohesion; gene expression; chromatin and epigenetics

DNA replication generates pairs of sister chromatids that are held together until anaphase by a protein complex named cohesin. The phenomenon, termed sister chromatid cohesion, is critical for the proper loading of chromatids onto mitotic and meiotic spindles. Defects in the cohesion pathway give way to chromosome instability that accompanies cancers and certain developmental diseases. In Roberts-SC phocomelia syndrome specifically, cohesion is strikingly absent from chromosomal domains bearing heterochromatin, a form of chromatin that was initially thought to package the “junk” DNA of eukaryotic genomes. Heterochromatin is now known to play critical roles in the nucleus, ranging from maintaining proper chromosome segregation to regulating gene expression at the level of transcription. Heterochromatin domains are distinguished at the molecular level by specialized histone modifications and non-histone binding proteins. The structure is passed from one generation to the next in a heritable manner that has become a paradigm of epigenetic control.

My lab has held a long-standing interest in the ways that heterochromatin is assembled, maintained and inherited. Our recent work includes focus on the specialized roles of heterochromatin in sister chromatid cohesion. We use the budding yeast Saccharomyces cerevisiae as a model eukaryotic system where we have developed molecular biological tools to ask questions at the mechanistic level.

Selected Publications

Chou, C.-C. Li, Y.-C. and Gartenberg, M. R. (2008). Bypasing the roles of Sir2 and O-acetyl-ADP-ribose in transcriptional silencing. Mol. Cell 31:650-659.

Valenzuela, L., Dhillon, N., Dubey, R. N., Gartenberg, M. R., and Kamakaka, R. T. (2008). Long-range communication between the silencers of HMR. Mol. Cell. Biol. 28:1924-35.

Dubey, R. N. & Gartenberg, M. R. (2007) A tDNA establishes cohesion of a neighboring silent chromatin domain. Genes Dev. 21:2150-2160.

Chang, C.-R., Wu, C.-S., Hom, Y., and Gartenberg, M. R. (2005). Targeting and maintenance of cohesin at transcriptionally silent chromatin. Genes Dev 19:3031-3042.

Gasser, S. M.,* Hediger, F., Taddei, A., Neumann, F. N., and Gartenberg, M. R. (2004). The function of telomere clustering in yeast: The Circe Effect. In Epigenetics, Cold Spring Harbor Symposia on Quantitative Biology, vol. 69. eds. B. Stillman and D. Stewart. New York, Cold Spring Harbor laboratory Press:327-338.

Gartenberg, M. R.,* Neumann, F. N., Laroche, T., Blaszczyk, M., and Gasser, S. M. (2004). Sir-mediated repression can occur independently of chromosomal and subnuclear contexts. Cell 119:955-967.

Andrulis, E. A., Zappulla, D. C., Ansari, A. I., Perrod, S., Laiosa, C. V., Gartenberg, M. R.,* and Sternglanz, R.* (2002). Esc1, a nuclear periphery protein required for Sir4-based plasmid anchoring and partitioning. Mol. Cell. Biol. 22:8292-8301.
*Corresponding Authors

Li, Y.-C., Cheng, T.-H., and Gartenberg, M. R. (2001). Establishment of transcriptional silencing in the absence of DNA replication. Science 291:650-653.

Gartenberg, M. R. (2000). The Sir proteins of Saccharomyces cerevisiae: mediators of transcriptional silencing and much more. Curr. Opin. Microbiol. 3:132-137.

Cheng, T.-H. and Gartenberg, M. R. (2000). Yeast heterochromatin is a dynamic structure that requires silencers continuously. Genes Dev. 14:452-463.