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Epigenetics is defined by the
organization of the eukaryotic genome within chromatin and the involvement
of this organization in the regulation of DNA metabolism (transcription,
replication, repair and recombination). This definition has been evolving
to encompass the many processes that cannot be accounted for by simple changes
in DNA sequence. Abnormalities of epigenetic mechanisms result in human
disorders that include developmental anomalies and cancer. The Magnuson
lab focuses on the role of mammalian polycomb-group proteins in unique epigenetic
phenomena such as genomic imprinting and X-chromosome inactivation. In addition,
the lab works on the role of mammalian SWI/SNF complexes, which displace
nucleosomes from promoter regions of target genes. Finally, to facilitate
functional genomic analyses, the Magnuson lab has also developed a genome-wide
mutagenesis strategy for mice. Mutagenesis has long been a fundamental tool
for the genetic analysis of experimentally tractable organisms such as yeast,
fruit flies, and nematodes. However, despite a long history of the mouse
as a model system for mammalian genetics, as well as a decade of gene-targeting
experiments, mutations exist for only a small percentage of its genes. The
lab has overcome the limitations of mutagenesis in the mouse by developing
methods capable of systematically generating mutations in all genes of totipotent
embryonic-stem (ES) cells. A mutagenized library of 4,000 clonal ES-cell
lines has been created, from which 15-25 alleles of any gene can be isolated.
Mice can then be derived from the mutagenized cells carrying anyone of the
alleles. Our goal is to create a comprehensive collection of variant alleles
for all genes in the mouse.
Selected Publications: Bultman SJ, Gebuhr TC, Pan H, Svoboda P, Schultz RM, Magnuson T. (2006) Maternal BRG1 regulates zygotic genome activation in the mouse. Genes Dev. 20:1744-54. Kalantry S, Magnuson T. (2006) The Polycomb group protein EED is dispensable for the initiation of random X-chromosome inactivation. PLoS Genet. 2:e66. Kalantry S, Mills KC, Yee D, Otte AP, Panning B, Magnuson T. (2006) The Polycomb group protein Eed protects the inactive X-chromosome from differentiation-induced reactivation. Nat Cell Biol. 8:195-202. Bultman SJ, Gebuhr TC, Magnuson T. (2005) A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in beta-globin expression and erythroid development. Genes Dev. 19:2849-61. Griffin CT, Trejo J, Magnuson T. (2005) Genetic evidence for a mammalian retromer complex containing sorting nexins 1 and 2. Proc Natl Acad Sci U S A. 102(42):15173-7. Montgomery
ND, Yee D, Chen A, Kalantry S, Chamberlain SJ, Otte AP, Magnuson T.
(2005) The murine polycomb group protein Eed is required
for global histone H3 lysine-27 methylation. Curr Biol. 15:942-7.
Austin CP, Battey JF, Bradley A, Bucan M, Capecchi M, Collins FS, Dove WF, Duyk G, Dymecki S, Eppig JT, Grieder FB, Heintz N, Hicks G, Insel TR, Joyner A, Koller BH, Lloyd KC, Magnuson T, Moore MW, Nagy A, Pollock JD, Roses AD, Sands AT, Seed B, Skarnes WC, Snoddy J, Soriano P, Stewart DJ, Stewart F, Stillman B, Varmus H, Varticovski L, Verma IM, Vogt TF, von Melchner H, Witkowski J, Woychik RP, Wurst W, Yancopoulos GD, Young SG, Zambrowicz B.(2004) The knockout mouse project. Nat Genet 36:921-924.
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contact information: [phone] [email] [website] |
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