Summary: | 碩士 === 國立中正大學 === 分子生物研究所 === 102 === During development, several transcription factors are found crucial for the formation of the pancreas. Among these factors, PDX1 plays a critical role in defining the region of the primitive gut that will form the pancreas; as a result, PDX1-deficient mice fail to develop pancreatic tissue.
To further understand the action of PDX1, we have utilized the yeast two-hybrid assay to screen an E10.5 pancreatic bud cDNA library using PDX1 as a bait. One of the identified gene is zinc finger protein 280d (Zfp280d) whose function has not been described before. There are three members in mice zinc finger protein 280 (Zfp280) family, including Zfp280b, Zfp280c and Zfp280d. Zfp280d contains nine zinc finger domains and a DUF4195 domain. Interestingly, the Zfp280d protein is very similar to Zfp280b and Zfp280c, except in its DUF4195 domain. Our lab has previously proved that Zfp280d interacts with PDX1 by pull-down and co-immunoprecipitation experiments. In addition, we have also shown that PDX1 and Zfp280d are co-localized in cell nucleus.
I have further characterized the interaction between Zfp280d and PDX1 and shown that only the DUF4195 domain in Zfp280d interacts with PDX1. We hypothesize that PDX1 might bring Zfp280d through its DUF4195 domain to activate or repress the expression of its downstream target genes. In addition, I have knockdowned the expression of Zfp280d in a β-cell line, NIT-1, and observed decreased expression of Pax6 and insulin. These results suggest Zfp280d may also play an important role in maintaining mature β-cell functions.
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