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PRINCIPAL SCIENTIST
Kohwi-Shigematsu, T
SCIENTISTS
Cai, S
POSTDOCTORAL FELLOWS
Han, H
Horike, S
RESEARCH ASSOCIATES
Kurano, L
STUDENTS
Mark, J
Chiu, W
Kim, G
Le, L
Miyano, M
Nakajima, Y
Nakayama, Y
Wu, K
STAFF
Staff Names Coming Soon
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The higher order structure of eukaryotic chromosomes consists
of independent loop domains, which are thought to be separated
from each other by the periodic attachment of specialized
genomic sequences (matrix attachment region or MARs) onto
the nuclear matrix. We study how proteins that specifically
bind to MARs regulate genomic DNA organization and cell
functions such as transcription and replication.
We previously identified a MAR-binding protein, SATB1. SATB1
consists of a novel class of DNA-binding proteins recognizing
a specific region with the high unwinding capability (BUR;
base unpairing region) typically found in MARs. SATB1 is
a cell-type specific MAR-binding protein, which is predominantly
expressed in thymocytes. SATB1 binds in vivo in thymocytes
and Jurkat T cells to specialized genomic DNA at the bases
of chromatin loop domains, the sites that are attached to
the nuclear matrix.
We demonstrated that SATB1 is an essential protein for
proper T-cell development, by establishing SATB1 knockout
mice. In SATB1-deficient thymocytes, multiple genes are
dysregulated. We are also currently studying the role of
SATB1 in T-cell apoptosis. BUR sequences are binding targets
of other MAR-binding proteins. We have characterized a series
of such proteins from human breast carcinomas. The MAR-binding
activity of these proteins was virtually undetectable in
normal breast tissues and in benign breast lesions but it
was strongly detectable in all breast carcinomas tested.
Our recent study shows that certain proteins from human
breast carcinomas make a protein complex and synergistically
bind to BURs. Some MAR-binding proteins may be critical
for the maintenance of breast cancer or other types of cancer.
Further research on these proteins may provide important
insights to cancer therapy in the future.
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Terumi Kohwi-Shigematsu
Senior Staff Scientist/
Life Sciences Division
One Cyclotron Rd.
Mailstop: 70A-1118
Berkeley, CA 94720
tel: (510)486-4983
fax: (510)486-4545
email: TKohwi-Shigematsu@lbl.gov
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Dickinson, L. A., Dickinson, C. D., and
Kohwi-Shigematsu, T. (1997) The nuclear matrix attachment
region (MAR)-binding protein SATB1 contains a homeodomain
that promotes specific recognition of the core unwinding element
of a MAR. J. Biol. Chem., 272, 11463-11470.
Kohwi-Shigematsu, T., Maass, K., and Bode, J. (1997) A thymocyte
factor SATB1 suppresses transcription of stably integrated
MAR-linked reporter genes. Biochemistry, 36: 12005-12010.
deBelle, I., Cai, S. and Kohwi-Shigematsu, T. (1998) The
genomic sequences bound to special AT-rich sequence-binding
protein 1 (SATB1) in vivo in Jurkat T cells are tightly associated
with the nuclear matrix at the bases of the chromatin loops.
J. Cell Biol., 141:335-348.
Galande, S. and Kohwi-Shigematsu,T. Poly(ADP-ribose) polymerase
and Ku autoantigen form a complex and synergistically bind
to matrix attachment sequences. J. Biol. Chem. in press.
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