Lab
Chung Lab
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Statement of Research Interest
The establishment of zebrafish model to study sex gland development
1. Steroidogenic Gene Regulation
We have been studying the regulation of genes involved in steroid hormone synthesis. One gene of interest is CYP21, which is defective in a common disease with steroid imbalance. In collaboration with physicians, we characterized the sites of mutations among Chinese population, designed methods for fast prenatal diagnosis, and studied the structure-function relationship of the protein. The severity of the disease correlates with the residual enzymatic activity of the mutated protein.
Another main focus is on the control of steroidogenic gene expression. Using both cell culture and transgenic mouse techniques, we have characterized cis-acting elements in a 2.3 kb fragment of the CYP11A1 gene which control gene expression in the adrenal and gonads, under the control of hormones in a developmentally regulated fashion.
Transcription factor SF1, a member of the Ftz-F1 family, activates steroidogenic gene expression. We dissected SF1 domains to show that a conserved Ftz-F1 box and the connecting proline-rich region is important for nuclear translocation and interaction with general transcription factor TFIIB.
2. Zebrafish Development
We have cloned zebrafish genes which play a role during development. Among them, sox9 is important probably for cartilage development and testis formation. We find the sox9 gene is duplicated in zebrafish. Sox9a and sox9b expression patterns differ, indicating their separate role during development.
Ftz-F1 is a nuclear receptor protein important for segmentation. We find that zebrafish Ftz-F1 gene has two promoters and is alternatively spliced, creating four transcripts. Ftz-F1 is mainly expressed in the somites, spinal cord, mandibula, and gut derivatives, indicating their possible function in these tissues.
Steroidogenic genes, such as CYP11A1, CYP19, and 3-beta-HSD, have also been cloned in our laboratory. They are expressed in the gonads and the brain of zebrafish, two sites important for steroid synthesis. It indicates that steroids may play a role during early development.
1. Steroidogenic Gene Regulation
We have been studying the regulation of genes involved in steroid hormone synthesis. One gene of interest is CYP21, which is defective in a common disease with steroid imbalance. In collaboration with physicians, we characterized the sites of mutations among Chinese population, designed methods for fast prenatal diagnosis, and studied the structure-function relationship of the protein. The severity of the disease correlates with the residual enzymatic activity of the mutated protein.
Another main focus is on the control of steroidogenic gene expression. Using both cell culture and transgenic mouse techniques, we have characterized cis-acting elements in a 2.3 kb fragment of the CYP11A1 gene which control gene expression in the adrenal and gonads, under the control of hormones in a developmentally regulated fashion.
Transcription factor SF1, a member of the Ftz-F1 family, activates steroidogenic gene expression. We dissected SF1 domains to show that a conserved Ftz-F1 box and the connecting proline-rich region is important for nuclear translocation and interaction with general transcription factor TFIIB.
2. Zebrafish Development
We have cloned zebrafish genes which play a role during development. Among them, sox9 is important probably for cartilage development and testis formation. We find the sox9 gene is duplicated in zebrafish. Sox9a and sox9b expression patterns differ, indicating their separate role during development.
Ftz-F1 is a nuclear receptor protein important for segmentation. We find that zebrafish Ftz-F1 gene has two promoters and is alternatively spliced, creating four transcripts. Ftz-F1 is mainly expressed in the somites, spinal cord, mandibula, and gut derivatives, indicating their possible function in these tissues.
Steroidogenic genes, such as CYP11A1, CYP19, and 3-beta-HSD, have also been cloned in our laboratory. They are expressed in the gonads and the brain of zebrafish, two sites important for steroid synthesis. It indicates that steroids may play a role during early development.
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