Molecular Cell & Developmental Biology
225 Sinsheimer Laboratories
Phone: 831.459.4986
Fax: 831.459.3139
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SUSAN STROME Professor of MCD Biology B.A., University of New Mexico, Albuquerque Ph.D., University of Washington, Seattle Postdoc, University of Colorado, Boulder   STROME LAB

225 Sinsheimer Laboratories University of California Santa Cruz, CA 95064 phone 831.459.4615 fax 831.459.3139 strome@biology.ucsc.edu office hours

Special properties of germ cells and stem cells

Germ cells (the cells that give rise to eggs and sperm) have special properties.  Their immortality allows them to be perpetuated from generation to generation, and their totipotency allows them to generate all of the diverse cells types of the body in each generation.  These features resemble the self-renewing and pluripotent features of stem cells.  In fact, mammalian germ cells have been shown to be a source of pluripotent stem cells. 

Our lab investigates the mechanisms used by germ cells to establish and maintain their identity, immortality, and totipotency.  We study germ cells in the model organism C. elegans using a wide variety of approaches, including forward genetics, RNAi, imaging, molecular biology, biochemistry, and whole genome microarray-based technologies.  Our current focus areas are control of gene expression in germ cells by regulation of packaging DNA into chromatin, and regulation of RNA metabolism by germline-specific cytoplasmic germ granules.

Chromatin regulation in C. elegans germ cells

A currently booming area of research is investigating how gene expression is regulated at the level of packaging DNA around histone octamers.  Covalent modifications of histone tails is one level at which this regulation occurs.  The C. elegans MES system regulates chromatin organization in germ cells and embryos.  Loss of any of the 4 MES proteins leads to germ cell death and sterility.  MES-2, MES-3, and MES-6 are the C. elegans version of the E(Z)-ESC complex or Polycomb Repressive Complex 2 (PRC2).  Like PRC2 across species, the MES-2/3/6 complex catalyzes a repressive histone modification, methylation of histone H3 on Lys27.  In worms, this complex concentrates H3Lys27 methylation on the X chromosomes and participates in keeping them in a silent state in germ cells.  In contrast to the X focus of MES-2/3/6 action, MES-4 is dramatically concentrated on the autosomes, where it methylates H3 on Lys36.  Despite its apparent absence from most of the X, removal of MES-4 leads primarily to desilencing of genes on the X.  We have formulated models for how MES-4 "acts at a distance" and cooperates with MES-2/3/6 in X silencing.  We are currently moving our analysis of MES binding and action from the chromosome level to the gene level, testing models for MES function, and screening to identify other proteins that collaborate with the MES's.  Our studies will contribute to understanding chromatin-level regulation of pluripotency and immortality, and how cells regulate the chromatin state of entire chromosomes, for instance during X-chromosome dosage compensation.

Defining functional chromatin elements through modENCODE

We recently joined forces with 6 other labs - Jason Lieb, Julie Ahringer, Abby Dernburg, Arshad Desai, Xiaole Liu, and Eran Segal - and with Nimblegen to analyze the distributions of lots of interesting chromatin modifications and chromatin regulators in C. elegans.  Our primary approach is chromatin immunoprecipitation followed by microarray (ChIP-chip) and bioinformatic analysis.  The model organism ENCODE projects will provide insights into regulation of DNA packaging and segregation and gene expression in worms and flies and will inform efforts to define functional elements in the human genome.

P granules as cytoplasmic RNA regulators

Germline-specific organelles termed "germ granules" are a common feature of germ cells across species.  They beautifully mark the germ lineage but their role in that tissue has remained mysterious.  We are dissecting the composition and functions of C. elegans germ granules, termed P granules.  We have defined a pathway of P-granule assembly involving three key proteins:  DEPS-1 stabilizes GLH-1, which in turn recruits PGL-1.  Loss of any of those proteins leads to sterility at elevated temperature.  Each of the three proteins is linked to RNA regulation:  GLH-1 and PGL-1 are predicted to bind RNA, DEPS-1 and PGL-1 (but not GLH-1) are required for RNA interference in the germ line, DEPS-1 may contribute to endo-siRNA regulation.  Most P granules overlie nuclear pores in the germ line, suggesting the additional possibility that P granules contribute to control of nuclear transport.  Our studies of P granules will contribute to understanding the special needs of germ cells, how germ granules help meet those needs, and features and functions of "RNA granules" in diverse cell types.

Selected Publications:

Takasaki, T., Z. Liu., Y. Habara, K. Nishiwaki, J. Nakayama, K. Inoue, H. Sakamoto, and S. Strome  (2007)  MRG-1, an autosome-associated protein, silences X-linked genes and protects germline immortality in C. elegans.  Development 134: 757-767.

Strome, S. and R. Lehmann  (2007)  Germ versus soma decisions - lessons from flies and worms. Science 316: 392-393.

Saunders, A.M., J. Powers, S. Strome, and W.M. Saxton.  (2007)  Kinesin-5 acts as a brake in anaphase spindle elongation.  Curr. Biol. 17: R453-454.

Bender, L.B., J. Suh, C.R. Carroll, Y. Fong, I.M. Fingerman, S.D. Briggs, R. Cao, Y. Zhang, V. Reinke, and S. Strome  (2006)  MES-4, an autosome-associated histone methyltransferase that participates in silencing the X chromosomes in the C. elegans germ line.  Development 133: 3907-3917.

Strome, S. and W. Kelly  (2006)  Epigenetic regulation of the X chromosomes in C. elegans.  In Epigenetics, D.C. Allis, T. Jenuwein, D. Reinberg (eds.), pp. 291-305.

Ketel, C.S., E.F. Anderson, M.L. Vargas, J. Suh, S. Strome, and J.A. Simon  (2005)  Subunit contributions to histone methyltransferase activities of fly and worm Polycomb group complexes.  Molec. Cell. Biol. 25: 6857-6868.

Schmidt, D., D. Rose, W. Saxton, and S. Strome  (2005)  Functional analysis of cytoplasmic dynein heavy chain in C. elegans with fast-acting temperature-sensitive mutations.  Molec. Biol. Cell 16: 1200-1212. 

Powers, J., D. Rose, A. Saunders, S. Dunkelbarger, S. Strome, and W. Saxton  (2004)  KLP-19 is required for polar exclusion force and for correct  chromosome segregation.  J. Cell Biol. 166: 991-1001.

Bender, L.B., R. Cao, Y. Zhang, and S. Strome  (2004)  The MES-2/MES-3/MES-6 complex and regulation of histone H3 methylation in C. elegans.  Curr. Biol. 14: 1639-1643.

Fong, Y., L. Bender, W. Wang, and S. Strome  (2002)  Regulation of the different chromatin states of autosomes and X chromosomes in the germline of C. elegans.  Science 296: 2235-2238.