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Regulation of human MAPT gene expression.

Caillet-Boudin ML, Buée L, Sergeant N, Lefebvre B - Mol Neurodegener (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Univ. Lille, UMR-S 1172, Inserm, CHU, 59000, Lille, France. marie-laure.caillet@inserm.fr.

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.

No MeSH data available.


Related in: MedlinePlus

Transcription initiation sites (black perpendicular arrow) and termination sites (simple gray arrow). These sites enable the expression of the complete Tau transcript/protein. For other sites, see Fig. 4b. Red numbers: initiation sites according to the database. Green numbers: initiation sites described in [77]. FS: forward strand, RS: reverse strand
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Fig3: Transcription initiation sites (black perpendicular arrow) and termination sites (simple gray arrow). These sites enable the expression of the complete Tau transcript/protein. For other sites, see Fig. 4b. Red numbers: initiation sites according to the database. Green numbers: initiation sites described in [77]. FS: forward strand, RS: reverse strand

Mentions: According to the technique used, several initiation sites for Tau transcription have been reported in both rats and humans [65, 77]. The human transcript sequences published in databases confirm the diversity of the transcription start sites. However, some discrepancies exist between the sites described in the literature and those in databases. In particular, the initiation sites of the published sequences are located in E0, whereas the Ensembl database shows that various initiation sites are present all along the gene in addition to those in E0 (Fig. 3, Fig. 4b) [125]. Three of these identified sites are common between the literature and databases.Fig. 4


Regulation of human MAPT gene expression.

Caillet-Boudin ML, Buée L, Sergeant N, Lefebvre B - Mol Neurodegener (2015)

Transcription initiation sites (black perpendicular arrow) and termination sites (simple gray arrow). These sites enable the expression of the complete Tau transcript/protein. For other sites, see Fig. 4b. Red numbers: initiation sites according to the database. Green numbers: initiation sites described in [77]. FS: forward strand, RS: reverse strand
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4499907&req=5

Fig3: Transcription initiation sites (black perpendicular arrow) and termination sites (simple gray arrow). These sites enable the expression of the complete Tau transcript/protein. For other sites, see Fig. 4b. Red numbers: initiation sites according to the database. Green numbers: initiation sites described in [77]. FS: forward strand, RS: reverse strand
Mentions: According to the technique used, several initiation sites for Tau transcription have been reported in both rats and humans [65, 77]. The human transcript sequences published in databases confirm the diversity of the transcription start sites. However, some discrepancies exist between the sites described in the literature and those in databases. In particular, the initiation sites of the published sequences are located in E0, whereas the Ensembl database shows that various initiation sites are present all along the gene in addition to those in E0 (Fig. 3, Fig. 4b) [125]. Three of these identified sites are common between the literature and databases.Fig. 4

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Univ. Lille, UMR-S 1172, Inserm, CHU, 59000, Lille, France. marie-laure.caillet@inserm.fr.

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.

No MeSH data available.


Related in: MedlinePlus