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

 


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.

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

 

 

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.