Julie A. Law
Ph.D. Biochemistry, The Johns Hopkins University School of Medicine
B. S. Magna cum laude Biochemistry and Biophysics, Oregon State University
"The expression of genetic information within each cell must be precisely
regulated for normal development, as is evident by the numerous diseases and
developmental defects associated with aberrant gene expression. One layer
of gene regulation involves the addition of chemical groups, or 'epigenetic modifications,'
to chromatin, a combination of DNA and proteins in a cell's nucleus. I
am interested in understanding how these chemical instructions are recognized
and translated into stable gene expression patterns."
In plants, mammals and other eukaryotic
organisms, the addition of epigenetic
modifications to both DNA and histones
(proteins that package and order DNA) are
known to influence the expression of the
underlying genes and to play critical roles
in diverse biological processes, including
cellular differentiation, development
and the maintenance of genome integrity.
However, compared to the amount of data
generated over the last few decades regarding
the proteins and pathways responsible
for establishing, maintaining and removing
epigenetic modifications, relatively little is
known about how epigenetic modifications
actually lead to changes in gene expression
and chromatin structure.
The plant Arabidopsis thaliana provides
an ideal system to study epigenetic processes.
It is genetically malleable, highly
amenable to whole genome analyses and,
unlike mammals, is highly tolerant of
dramatic changes to its epigenetic code.
In addition, plants and mammals share
many of the key proteins and pathways
involved in establishing and maintaining
epigenetic modifications, so findings in
plants may be applicable to animals and
humans. To gain a better understanding of
the cascade of events that lead from the
addition or removal of a particular epigenetic
modification into a change in gene
expression, Law focuses on the characterization
of several newly identified families
of chromatin binding proteins. By employing
genetic, biochemical and genomic
approaches, she aims to determine the
epigenetic modifications recognized by
these protein families, identify their interacting
partners and determine their effects
on gene expression and higher order chromatin
structure. This will provide a holistic
view of how epigenetic modifications control
Such studies will begin filling a gap in our
current understanding of epigenetic gene
regulation and will greatly enhance our
ability to understand and control the expression
of existing and newly introduced
genes, which has broad implications in
both agriculture and gene therapy.
Awards and Honors
- Ruth L. Kirschstein National Research Service Award, National Institute of Health (2007-2010)
- Howard Hughes Medical Institute Summer Fellowship, Oregon State University (2000)
Law, J.A., Vashisht, A.A., Wohlschlegel, J.A. & Jacobsen, S.E. 2011. SHH1, a Homeodomain Protein Required for DNA Methylation, As Well As RDR2, RDM4, and Chromatin Remodeling Factors, Associate with RNA Polymerase IV. PLoS Genet 7, e1002195.
Rajakumara, E.*, Law, J.A.*, Simanshu, D.K., Voigt, P., Johnson, L.M., Reinberg, D., Patel, D.J., and Jacobsen, S.E. 2011. A dual flip out mechanism for 5mC recognition by the Arabidopsis SUVH5 SRA domain and its impact on DNA methylation and H3K9 dimethylation in vivo Genes Dev 25(2):137-152.
*The first two authors contributed equally to this publication
Greenberg, M.V., Ausin, I., Chan, S.W., Cokus, S.J., Cuperus, J.T., Feng, S., Law, J.A., Chu, C., Pellegrini, M., Carrington, J.C., and Jacobsen, S.E. 2011. Identification of genes required for de novo DNA methylation in Arabidopsis. Epigenetics 6(3).
Guo, L., Yu, Y., Law, J.A., and Zhang, X. 2010. SET DOMAIN GROUP2 is the major histone H3 lysine 4 trimethyltransferase in Arabidopsis. Proc Natl Acad Sci U S A 107(43): 18557-18562.
Law, J.A., Ausin, I., Johnson, L.M., Vashisht, A.A., Zhu, J.K., Wohlschlegel, J.A., and Jacobsen, S.E. 2010. A protein complex required for polymerase V transcripts and RNA- directed DNA methylation in Arabidopsis. Curr Biol 20(10): 951-956.
Law, J.A. and Jacobsen, S.E. 2010. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet 11(3): 204-220.
Law, J.A. and Jacobsen, S.E. 2009. Molecular biology. Dynamic DNA methylation. Science 323(5921): 1568-1569.
Johnson, L.M., Law, J.A., Khattar, A., Henderson, I.R., and Jacobsen, S.E. 2008. SRA-domain proteins required for DRM2-mediated de novo DNA methylation. PLoS Genet 4(11): e1000280.
Law, J.A., O'Hearn, S.F., and Sollner-Webb, B. 2008. Trypanosoma brucei RNA editing protein TbMP42 (band VI) is crucial for the endonucleolytic cleavages but not the subsequent steps of U-deletion and U-insertion. RNA 14(6): 1187-1200.
Law, J.A., O'Hearn, S., and Sollner-Webb, B. 2007. In Trypanosoma brucei RNA editing, TbMP18 (band VII) is critical for editosome integrity and for both insertional and deletional cleavages. Mol Cell Biol 27(2): 777-787.
Zhelonkina, A.G., O'Hearn, S.F., Law, J.A., Cruz-Reyes, J., Huang, C.E., Alatortsev, V.S., and Sollner-Webb, B. 2006. T. brucei RNA editing: action of the U-insertional TUTase within a Udeletion cycle. RNA 12(3): 476-487.
Law, J.A., Huang, C.E., O'Hearn, S.F., and Sollner-Webb, B. 2005. In Trypanosoma brucei RNA editing, band II enables recognition specifically at each step of the U insertion cycle. Mol Cell Biol 25(7): 2785-2794.
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