Becky Pferdehirt - Graduate Student

131 Koshland Hall
(510) 643-5583
beckyp@berkeley.edu

Mailing Address:
University of California Berkeley
16 Barker Hall, MC 3204
Berkeley, CA 94720-3204

X-chromosome dosage compensation is an essential, chromosome-wide regulatory mechanism that balances gene expression between sexes with differing numbers of sex chromosomes (e.g. XX female, XY/XO male). In C. elegans, dosage compensation is executed by a multi-protein complex that resembles condensin, a conserved complex involved in chromosome compaction, resolution and segregation. This dosage compensation complex (DCC) binds both X chromosomes of XX animals to decrease X transcript levels by approximately two-fold. The DCC binds to at least two categories of sites on X. rex sites recruit the DCC in an autonomous manner whereas dox sites fail to bind the DCC when detached from X. Genome-wide studies revealed that while the DCC is greatly enriched on the X chromosome, it is also found bound to sites throughout the genome. Precisely how the DCC differentiates the X chromosome from autosomes, how binding requirements at rex, dox and autosomal sites differ, and how the DCC reduces gene expression once bound are all questions fundamental to our understanding of dosage compensation addressed by my thesis work.

I have discovered that post-translational modification by the small ubiquitin-like molecule SUMO is essential for proper targeting of the DCC to X and that multiple DCC components are targets of sumoylation. I have also described fundamental differences in the principles by which the DCC recognizes and binds rex, dox and autosomal sites. DCC binding to rex sites requires the recruitment proteins SDC-2, SDC-3 and DPY-30, whereas dox sites posses a low-level intrinsic binding similar to that of autosomes independently of these proteins. The proximity in cis of rex sites to dox promotes full dox site binding and distinguishes dox sites from autosomal sites. Finally, I have shown for the first time that In C. elegans dosage compensation acts at least in part at the level of transcription.

Presentations:

"Targeting the Condensin-like Dosage Compensation Complex to X"
International C. elegans Meeting, UCLA, June 2009

"Targeting the Condensin-like Dosage Compensation Complex to X"
UC Berkeley Cell and Developmental Biology Retreat. Grandlibackken, Tahoe City CA. September 2009

"Targeting the Dosage Compensation Complex to X chromosomes"
Genetics and Development Division Retreat, Granlibackken, Tahoe City, CA. October 2007

Posters:

"Sumoylation is required for accurate targeting of the C. elegans Dosage Compensation Complex to X"
Keystone Symposia on The Molecular Basis for Chromatin Structure and Regulation, Taos NM, January 2010

Investigating the role of the Tip60 complex in C. elegans Dosage Compensation

International C. elegans Meeting, UCLA, CA. June 2007.

Publications:

Pferdehirt, R. R., Kruesi, W. S., Meyer, B. J.   "An MLL/COMPASS subunit functions in the C. elegans dosage compensation complex to target X chromosomes for transcriptional regulation of gene expression." Genes & Development 25(5) (2011): 499-515.

Jans, J. Gladden, J. M., Ralston, E. J., Pickle, C. S., Michel, A. H., Pferdehirt, R. R., Eisen, M. B., Meyer, B. J.   "A condensin-like dosage compensation complex acts at a distance to control expression throughout the genome." Genes & Development 23 (2009): 602-618.

M. Slater, M.R., Hurst, M., Pferdehirt, B., White, D., Niles, A., Betz, N., Schenborn. “Expression of soluable native human proteins in cell-free extracts.” Promega Notes (“P Notes”) 91 (2005): 21-25.

M. Slater, M., Hartnett, J., Betz, N., Engligh, J., Strauss, E., Pferdehirt, B., Schenborn, E. “Introducing the Flexi® Vector System: A new system for cloning and expressing protein-coding regions.” Promega Notes 89 (2005): 11-15.

R. Somberg, R., Pferdehirt, B., Kupcho, K. “Kinase-Glo™ luminescent kinase assay: detect virtually any kinase.” Cell Notes 5 (2003): 5-8.

R. Somberg, R., Pferdehirt, B., Kupcho, K. “A universal kinase assay for a world of kinases.” Promega Notes 83 (2003): 14-17.

Funding Awards:

Recipient of the Genentech Foundation Fellowship 2009-2010