The molecular characterization of mouse caudal-related homeobox factors.

Format:

Book

Thesis/Dissertation

Author/Creator:

Taylor, Jennifer K.

Contributor:

University of Pennsylvania.

Language:

English

Subjects (All):

Molecular biology.

0307.

Local Subjects:

0307.

Physical Description:

155 pages

Contained In:

Dissertation Abstracts International 58-11B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

The complex mechanisms regulating intestinal development and differentiation are not well understood. Through the analysis of regulatory regions of two intestine-specific genes, sucrase isomaltase and intestinal phospholipase A/lysophospholipase, the processes that control cellular renewal, cell lineage allocation, and tissue restricted gene expression can be explored. Using this approach, a family of caudal-related homeobox (Cdx) proteins has been identified as factors that can regulate intestine-specific gene expression. Based on evidence from experiments with knockout mice, over-expression in cell lines, and characterization of intestinal tumors, the Cdx factors appear to be required for the maintenance of proper gut homeostasis. The biochemical and molecular characterization of the Cdx proteins provides insight into the mechanisms by which these proteins regulate intestinal development and differentiation. From work presented here, it is apparent that Cdx proteins bind to monomer and dimer DNA elements in a non-cooperative manner. Transient transfection analysis has demonstrated that these proteins function as transcriptional activators and can activate transcription from proximal and distal regulatory elements in a cell line restricted fashion. The activation domains of these proteins have been mapped and shown to localize to nonconserved regions in the amino terminal end of the proteins. The possibility that the Cdx proteins require a cofactor for activation was examined by studying the interaction of CBP, a well characterized coactivator, with the Cdx proteins. CBP was shown to physically interact with multiple domains in Cdx proteins, and it can modulate the ability of Cdx proteins to activate transcription. Taken together, this study characterized the ability of Cdx proteins bind DNA, activate intestine-specific gene expression, and interact with the CBP coactivator. These findings will be relevant to the understanding of how the Cdx family of proteins regulate the development and differentiation of the intestine and their potential role in intestine tumorigenesis.

Notes:

Source: Dissertation Abstracts International, Volume: 58-11, Section: B, page: 5810.

Thesis (Ph.D.)--University of Pennsylvania, 1997.

Local Notes:

School code: 0175.

ISBN:

9780591659641

Access Restriction:

Restricted for use by site license.