Class of 1970 Chancellor's Professor
Ph.D., University of Washington, 1979
Postdoctoral Fellow, University of Colorado-Boulder, 1979-84

Phone: 812/855-5450
Fax: 812/855-6705
Email Susan

Strome Lab website

Overview
During animal development, the germ line serves the unique and critical role of producing gametes and offspring.  To serve this role, germ cells require mechanisms to protect their “totipotency” and “immortality”.  How do primordial germ cells acquire and preserve these and other germline traits?  We are addressing this question in the model animal system, C. elegans, focusing on two regulatory systems: regulators of chromatin organization that are required for germline immortality, and unique cytoplasmic organelles that are required for proliferation and development of germ cells. 

C. elegans
C. elegans is a small (~1 mm) worm that lives in the soil and can be maintained in the lab by growth on bacteria.  The adult worm contains only ~1000 somatic cells and ~1000 germ cells, organized into a relatively simple body plan.  Sequencing of the worm genome has provided access to all of its ~20,000 genes, and we have both forward genetics and reverse genetic strategies such as RNAi to knock out selected genes and study the consequences.

MES proteins and chromatin regulation
Through genetic screens we identified mes-2, mes-3, mes-4, and mes-6 as being essential for germline immortality:  in the absence of a maternal supply of mes gene products, the nascent germ line dies.  MES-2 and MES-6 are homologous to the Polycomb Group proteins E(Z) and ESC, which bind one another and function as chromatin regulators in insects and vertebrates.  MES-2 and MES-6 form a complex with the novel protein MES-3.  MES-4, a homolog of mammalian NSD1, appears to function independently of the other MES proteins.  How do the MES proteins contribute to germline immortality?  Studies from the Reinke and Kelly labs demonstrated a remarkable property of the C. elegans germ line: the X chromosomes are globally silenced during most stages of development.  The MES proteins participate in that silencing, as evidenced by chromosome staining experiments and more recently by microarray analysis of gene expression patterns in gonads dissected from mes mutants.  The MES-2/3/6 complex participates, probably directly, in X silencing by concentrating a repressive histone modification (methylation of Lys 27 on histone H3, abbreviated H3K27me) on the Xs.  MES-4 participates in X silencing indirectly, by coating the autosomes and catalyzing a different histone modification (methylation of Lys36 on histone H3 or H3K36me).  We think that MES-4 and/or its methyl mark repel a repressor and help focus repressor action on the Xs (see model).  This system illustrates how chromatin modifiers can work in concert to achieve whole-chromosome regulation, and it focuses our attention on the X:autosome distinction.  We are current addressing the following questions:  To what chromosomal sites do the MES proteins bind?  How are the MES proteins targeted to those sites?  How do the methyl marks catalyzed by MES-2/3/6 and by MES-4 cause their respective effects on chromatin?  Why do the primordial germ cells in mes mutant larvae die?  It is an exciting time in both the chromatin field and the germline field – we are enjoying working at the intersection of the two areas. 

P granules and control of RNA
"Germ granules" are distinctive organelles found in the germ cells of many species, including C. elegans.  They have been invoked as "instructors" of germline development ever since their dramatic segregation to the germ line was first observed in fruit flies, frogs, and nematodes.  We have demonstrated that the germ granules in C. elegans (a.k.a. P granules) are indeed required for fertility.  The list of constitutive P-granule proteins currently includes PGL-1, PGL-2, PGL-3, GLH-1, GLH-2, GLH-3, GLH-4, and IFE-1.  All 8 proteins are predicted to bind RNA and several have been shown to be required for germline development.  The PGL proteins function redundantly, PGL-1 being the most critical – its loss leads to sterility but only at elevated temperature.  Similarly, the GLH proteins function redundantly, GLH-1 being the most critical – like PGL-1, loss of GLH-1 leads to sterility but only at elevated temperature.  Now that we have deletion alleles of all pgl and glh genes, we can finally eliminate the functions of both gene families and determine the effects on P-granule structure and on germline development.  IFE-1 is one of the 5 nematode isoforms of eIF4E, the component of the translation initiation complex that binds to mRNA caps.  IFE-1 is specifically required for spermatogenesis.  The current working model is that germ granules control the trafficking, translation, and/or stability of mRNAs in the germline.  Current projects in the lab are aimed at identifying additional P-granule components, defining the pathway of granule assembly, elucidating the roles of individual granule components, and using microarray analysis to investigate RNA regulation.  Our studies will provide a better understanding of the composition and functions of these intriguing and still mysterious germline-specific organelles.

Saunders, A.M., J. Powers, S. Strome, and W.M. Saxton. 2007. Anaphase spindle elongation: A molecular motor acts as a brake. Curr. Biol., in press.

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

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 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.

Strome, S. and W. Kelly.  2006.  Epigenetic regulation of the X chromosomes in C. elegans.  Cold Spring Harbor textbook on Epigenetics, In press.

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.

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. 

Strome, S.  2005.  Specification of the germ line.  In WormBook, The C. elegans Research Community, ed.  http://www.wormbook.org.

Li, S.,  C. M. Armstrong, N. Bertin, H. Ge1, S. Milstein, M. Boxem, P.O. Vidalain, J. Han, A. Chesneau1, T. Hao, D.S. Goldberg, Ning Li1, M. Martinez, J.-F. Rual1, P. Lamesch, L. Xu, M. Tewari, S.L. Wong, L.V. Zhang, G.F. Berriz, L. Jacotot, P. Vaglio, J. Reboul1, T. Hirozane-Kishikawa, Q. Li, H.W. Gabel, A. Elewa, B. Baumgartner, D.J. Rose, H. Yu, S. Bosak, R. Sequerra, A. Fraser, S.E. Mango, W.M. Saxton, S. Strome, S. Heuvel, F.Piano, J. Vandenhaute, C. Sardet, M. Gerstein, L. Doucette-Stamm, K.C. Gunsalus, J.W. Harper, M.E. Cusick, F.P. Roth, D.E. Hill, M. Vidal.  2004.   A Map of the Interactome Network of the Metazoan C. elegans.  Science 303: 540-543.