title: Regulation of human MAPT gene expression.
abstract: The number of known pathologies involving deregulated Tau expression/metabolism is increasing. Indeed, in addition to tauopathies, which comprise approximately 30 diseases characterized by neuronal aggregation of hyperphosphorylated Tau in brain neurons, this protein has also been associated with various other pathologies such as cancer, inclusion body myositis, and microdeletion/microduplication syndromes, suggesting its possible function in peripheral tissues. In addition to Tau aggregation, Tau deregulation can occur at the expression and/or splicing levels, as has been clearly demonstrated in some of these pathologies. Here, we aim to review current knowledge regarding the regulation of human MAPT gene expression at the DNA and RNA levels to provide a better understanding of its possible deregulation. Several aspects, including repeated motifs, CpG island/methylation, and haplotypes at the DNA level, as well as the key regions involved in mRNA expression and stability and the splicing patterns of different mRNA isoforms at the RNA level, will be discussed.
authors.affiliation: Univ. Lille, UMR-S 1172, Inserm, CHU, 59000, Lille, France. marie-laure.caillet@inserm.fr.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Caillet-Boudin
authors.affiliation: Univ. Lille, UMR-S 1172, Inserm, CHU, 59000, Lille, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.affiliation: Univ. Lille, UMR-S 1172, Inserm, CHU, 59000, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sergeant
authors.affiliation: Univ. Lille, UMR-S 1172, Inserm, CHU, 59000, Lille, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lefebvre
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D018899:CpG Islands; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D004251:DNA Transposable Elements; D005333:Fetus / Q000378:metabolism; D005786:Gene Expression Regulation; D006239:Haplotypes; D006801:Humans; D018895:Microsatellite Repeats; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012326:RNA Splicing; D020871:RNA Stability; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site; D016875:tau Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D004251:DNA Transposable Elements; C054369:MAPT protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors; D016875:tau Proteins; D004247:DNA