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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

Organization of the rat, mouse and human Tau promoters. The lengths of the various regions of the promoter are not representative of their precise localizations but are dependent on the cloning technique. Thus, differences in the length of a determined region among species are not significant. Note the influence of allelic variants on promoter activity. CpG islands present in the promoter are indicated
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Fig2: Organization of the rat, mouse and human Tau promoters. The lengths of the various regions of the promoter are not representative of their precise localizations but are dependent on the cloning technique. Thus, differences in the length of a determined region among species are not significant. Note the influence of allelic variants on promoter activity. CpG islands present in the promoter are indicated

Mentions: As determined by CpG Islands Track Settings (UCSC), one long CpG island spans approximately 300 nt upstream to 3000 nt downstream of E0 in human MAPT (the total [G + C] increases to 75 % around the transcription start site, with as high as 10 % CpG dimers) [76–78]. This CpG island (CpG300) is located in the promoter region (Fig. 1, Fig. 2). Two additional but more limited sequences are present, including one containing 27 CpGs (CpG27) that is located 13 kb upstream of E1 and another containing 21 CpGs (CpG21) that is located immediately upstream of E4A (UCSC Genome Browser [79]). The CpG21 island is situated at the beginning of the short transcript MAP-010/ENST00000576238 (Fig. 1, Fig. 4b). Thus, we cannot ignore the possibility that this CpG island may be involved in the transcriptional regulation of this minor transcript (see section 3.1.3). However, no histone H3 lysine 4 trimethylation, another feature of promoter regions, was found in this third CpG island (CpG21) using CpG Islands Track Settings (UCSC genome browser) [76, 80]. In addition to these three CpG islands, other CpG islands can be identified using less restrictive conditions. For example, one CpG island was identified in exon E9 (198 nt/266) using MethPrimer (http://www.urogene.org/methprimer) [75, 81]. This type of CpG island is a 3′ island as defined by Gardiner-Garden and Frommer [76]; however, no methylation studies of this type of island have been reported. Another CpG island has been predicted in the coding region of the last exon, E13, using the same MethPrimer tool [81].Fig. 2


Regulation of human MAPT gene expression.

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

Organization of the rat, mouse and human Tau promoters. The lengths of the various regions of the promoter are not representative of their precise localizations but are dependent on the cloning technique. Thus, differences in the length of a determined region among species are not significant. Note the influence of allelic variants on promoter activity. CpG islands present in the promoter are indicated
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Organization of the rat, mouse and human Tau promoters. The lengths of the various regions of the promoter are not representative of their precise localizations but are dependent on the cloning technique. Thus, differences in the length of a determined region among species are not significant. Note the influence of allelic variants on promoter activity. CpG islands present in the promoter are indicated
Mentions: As determined by CpG Islands Track Settings (UCSC), one long CpG island spans approximately 300 nt upstream to 3000 nt downstream of E0 in human MAPT (the total [G + C] increases to 75 % around the transcription start site, with as high as 10 % CpG dimers) [76–78]. This CpG island (CpG300) is located in the promoter region (Fig. 1, Fig. 2). Two additional but more limited sequences are present, including one containing 27 CpGs (CpG27) that is located 13 kb upstream of E1 and another containing 21 CpGs (CpG21) that is located immediately upstream of E4A (UCSC Genome Browser [79]). The CpG21 island is situated at the beginning of the short transcript MAP-010/ENST00000576238 (Fig. 1, Fig. 4b). Thus, we cannot ignore the possibility that this CpG island may be involved in the transcriptional regulation of this minor transcript (see section 3.1.3). However, no histone H3 lysine 4 trimethylation, another feature of promoter regions, was found in this third CpG island (CpG21) using CpG Islands Track Settings (UCSC genome browser) [76, 80]. In addition to these three CpG islands, other CpG islands can be identified using less restrictive conditions. For example, one CpG island was identified in exon E9 (198 nt/266) using MethPrimer (http://www.urogene.org/methprimer) [75, 81]. This type of CpG island is a 3′ island as defined by Gardiner-Garden and Frommer [76]; however, no methylation studies of this type of island have been reported. Another CpG island has been predicted in the coding region of the last exon, E13, using the same MethPrimer tool [81].Fig. 2

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