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Expression of the Synaptotagmin I Gene Is Enhanced by Binding of the Pituitary-Specific Transcription Factor, POU1F1

Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, Oregon 97239

Address all correspondence and requests for reprints to: Richard A. Maurer, Department of Cell and Developmental Biology, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97239. E-mail: maurerr{at}ohsu.edu.

The POU1F1 transcription factor (also known as Pit-1/GHF1) is required for development of pituitary cells that secrete prolactin, GH, and TSH. Presumably, POU1F1 regulates the expression of multiple genes required for expansion and differentiation of these pituitary cell lineages. However, only a few genes regulated by POU1F1 have been identified. In the present studies we have identified synaptotagmin I (Syt1) as a target gene for POU1F1 in GH₃ pituitary cells. Chromatin immunoprecipitation assays have provided evidence that POU1F1 binds close to the Syt1 exon that contains the initiation codon. Although this exon has previously been considered to be located far from the transcription initiation site, transcript mapping in GH₃ cells indicates that Syt1 mRNA synthesis is initiated close to the mapped POU1F1-binding site. POU1F1 knockdown studies using a short hairpin RNA vector have provided evidence that POU1F1 plays a role in stimulating expression of the endogenous Syt1 gene. Transfection studies with a Syt1-luciferase reporter gene are consistent with the presence of an internal, POU1F1-regulated promoter in the Syt1 gene. In vitro binding studies have provided further evidence for a POU1F1-binding site within this region of the Syt1 gene. Overall the studies provide evidence that Syt1 is a target gene regulated by POU1F1 in GH₃ pituitary cells. Because SYT1 has been extensively studied as an important transducer of Ca²⁺ signaling in regulated secretion, it seems likely that activation of Syt1 gene expression is part of a mechanism mediating POU1F-induced differentiation of pituitary cells.