title: Structure and evolution of the human SPRR3 gene: implications for function and regulation.
abstract: SPRR3, a member of the SPRR family of cornified envelope precursor proteins, is expressed in oral and esophageal epithelia, where it is strictly linked to keratinocyte terminal differentiation. This gene is characterized by intragenic duplications that have created the characteristic proline-rich repeats in the coding sequence, an alternative noncoding exon, and a 200-bp polypyrimidine tract in the promoter region. Mutational analysis of the promoter region and transient transfection in normal human keratinocytes showed that in addition to the polypyrimidine tract, multiple regulatory elements are involved in differentiation-specific expression. These elements include a high-affinity Ets binding site bound by ESE-1, an AP-1 site (TRE) recognized by the Jun/Fos family of transcription factors, and an ATF/CRE bound by Jun/Fos and ATF factors. The repositioning of the SPRR3 Ets binding site during evolution has a major effect on the relative contribution of this site to promoter activity.
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Leiden, 2300 RA, The Netherlands.
authors.forename: D F
authors.initials: DF
authors.lastname: Fischer
authors.forename: M W
authors.initials: MW
authors.lastname: Sark
authors.forename: M M
authors.initials: MM
authors.lastname: Lehtola
authors.forename: S
authors.initials: S
authors.lastname: Gibbs
authors.forename: P
authors.initials: P
authors.lastname: van de Putte
authors.forename: C
authors.initials: C
authors.lastname: Backendorf
mesh_terms: D051698:Activating Transcription Factor 2; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D002874:Chromosome Mapping; D055233:Cornified Envelope Proline-Rich Proteins; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004247:DNA; D004268:DNA-Binding Proteins; D019143:Evolution, Molecular; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides; D055232:Proline-Rich Protein Domains; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D012045:Regulatory Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051698:Activating Transcription Factor 2; D055233:Cornified Envelope Proline-Rich Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C105529:ELF3 protein, human; D010455:Peptides; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; C112254:SPRR3 protein, human; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004247:DNA