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• W1576194964 abstract "Abstract The CC2D1A / Freud‐1 gene has recently been linked to non‐syndromic mental retardation and a short isoform of mouse Five prime REpressor Under Dual repression binding protein 1 (Freud‐1) can repress the serotonin‐1A (5‐HT1A) receptor gene in rodent cells. In this study, we addressed the expression, localization and regulation of the human 5‐HT1A receptor gene by a long isoform of human Freud‐1 protein (Freud‐1 L ). We show that human CC2D1A/Freud‐1 RNA is expressed in brain and peripheral tissues and encodes short and long isoforms, which differ by an upstream in‐frame translational start site. Whereas previous studies identified the short isoform of Freud‐1 as the predominant isoform in rodent cells, we demonstrate that the long isoform is more abundant in human cells, especially in the nuclear fraction. The nuclear localization of Freud‐1 L was enriched upon inhibition of chromosome region maintenance 1/exportin 1‐dependent nuclear export, indicating a dynamic regulation of Freud‐1 nuclear localization. Consistent with a functional role in the nucleus, human Freud‐1 L bound specifically to its dual repressor element in the 5‐HT1A receptor gene in vitro and repressed transcription from these sites. Importantly, chromatin immunoprecipitation using antibodies specific for human Freud‐1 L demonstrated that it is bound to the dual repressor element in chromatin, indicating a functional role in regulating the basal expression of the 5‐HT1A receptor gene. Taken together, these results indicate that both the short and long isoforms of Freud‐1 are expressed, although Freud‐1 L is the major isoform that regulates the human 5‐HT1A receptor gene. Disruption of transcriptional regulation by mutation of Freud‐1 may play a role in abnormal brain function leading to mental retardation." @default.
• W1576194964 created "2016-06-24" @default.
• W1576194964 creator A5002795098 @default.
• W1576194964 creator A5024214967 @default.
• W1576194964 date "2007-08-01" @default.
• W1576194964 modified "2023-10-10" @default.
• W1576194964 title "The mental retardation gene CC2D1A/Freud-1 encodes a long isoform that binds conserved DNA elements to repress gene transcription" @default.
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• W1576194964 doi "https://doi.org/10.1111/j.1460-9568.2007.05727.x" @default.
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