CIDE-B Gene, Cell-specific Expression-control Study, And LPTS Regions Of The Genome Transcriptional Regulatory Elements S / MAR Research

The thesis consists of two parts. The first part is Dual promoters control the cell-specificexpression of the human cell death-inducing DFF45-like effector B gene, the second part isIdentification and characterization of Scaffold/Matrix Attachment Regions mapping on theLPTS gene locus at human chromosome 8p23.Cell death-inducing DFF45-like effector B (CIDE-B) is a member of the CIDE family ofapoptosis-inducing factors. The highly restricted pattern of expression of CIDE-B in the liverand spleen suggests that a mechanism exists for the tissue-and cell-specific regulation oftranscription of this gene. We present an analysis of the regulatory region of the humanCIDE-B gene, and we demonstrate here that the cell-specific expression of two transcripts ofCIDE-B is driven by upstream and internal promoters by an epigenetic and a geneticmechanism, respectively. Expression of the long transcript is regulated by DNA methylation ofthe upstream promoter region, while that of the short transcript is activated by HNF4α viainteraction with its response element (RE) in the internal promoter. Our results also show thatSp1 and Sp3 are key regulators that are required for basal activation of both promoters. Ourresults suggest a complex model for cell-specific transcriptional regulation of the humanCIDE-B gene, which involves epigenetic and genetic control of two different respectivepromoters.Scaffold/Matrix attachment regions (S/MARs) have higher affinity to nuclear matricesand organize eukaryotic chromatin into the loop structure. The gene for LPTS is recentlyidentified as a novel putative tumor suppressor gene. Here, we identify the S/MARs within the162 kb LPTS gene locus. 5 S/MARs are demonstrated with high matrix-binding affinity, andone intronic S/MAR is found to stimulate expression of reporter gene in an orientationdependent way in the stable gene transfection assay. These studies provide an initial work foraccessing the potential roles of S/MARs in controlling gene activity and/or chromatin structurein this gene region.