ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator.
Identifieur interne : 000027 ( Main/Exploration ); précédent : 000026; suivant : 000028ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator.
Auteurs : Arne Jahn [Allemagne] ; Grishma Rane [Singapour] ; Maciej Paszkowski-Rogacz [Allemagne] ; Sergi Sayols [Allemagne] ; Alina Bluhm [Allemagne] ; Chung-Ting Han [Allemagne] ; Irena Draškovi [France] ; José Arturo Londo O-Vallejo [France] ; Alan Prem Kumar [Singapour] ; Frank Buchholz [Allemagne] ; Falk Butter [Allemagne] ; Dennis Kappei [Allemagne]Source :
- EMBO reports [ 1469-3178 ] ; 2017.
Abstract
Telomeres constitute the ends of linear chromosomes and together with the shelterin complex form a structure essential for genome maintenance and stability. In addition to the constitutive binding of the shelterin complex, other direct, yet more transient interactions are mediated by the CST complex and HOT1/HMBOX1, while subtelomeric variant repeats are recognized by NR2C/F transcription factors. Recently, the Kruppel-like zinc finger protein ZBTB48/HKR3/TZAP has been described as a novel telomere-associated factor in the vertebrate lineage. Here, we show that ZBTB48 binds directly both to telomeric and to subtelomeric variant repeat sequences. ZBTB48 is found at telomeres of human cancer cells regardless of the mode of telomere maintenance and it acts as a negative regulator of telomere length. In addition to its telomeric function, we demonstrate through a combination of RNAseq, ChIPseq and expression proteomics experiments that ZBTB48 acts as a transcriptional activator on a small set of target genes, including mitochondrial fission process 1 (MTFP1). This discovery places ZBTB48 at the interface of telomere length regulation, transcriptional control and mitochondrial metabolism.
DOI: 10.15252/embr.201744095
PubMed: 28500257
Affiliations:
- Allemagne, France, Singapour
- District de Dresde, Rhénanie-Palatinat, Saxe (Land)
- Dresde, Mayence
- Université nationale de Singapour
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sort="Londo O Vallejo, Jose Arturo" uniqKey="Londo O Vallejo J" first="José Arturo" last="Londo O-Vallejo">José Arturo Londo O-Vallejo</name><affiliation wicri:level="1"><nlm:affiliation>Telomeres & Cancer Laboratory, UMR3244, Institut Curie-CNRS-UPMC, Paris Cedex 05, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Telomeres & Cancer Laboratory, UMR3244, Institut Curie-CNRS-UPMC, Paris Cedex 05</wicri:regionArea><wicri:noRegion>Paris Cedex 05</wicri:noRegion><wicri:noRegion>Paris Cedex 05</wicri:noRegion></affiliation></author><author><name sortKey="Kumar, Alan Prem" sort="Kumar, Alan Prem" uniqKey="Kumar A" first="Alan Prem" last="Kumar">Alan Prem Kumar</name><affiliation wicri:level="4"><nlm:affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Cancer Science Institute of Singapore, National University of Singapore, Singapore City</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Buchholz, Frank" sort="Buchholz, Frank" uniqKey="Buchholz F" first="Frank" last="Buchholz">Frank Buchholz</name><affiliation wicri:level="3"><nlm:affiliation>Medical Systems Biology, UCC, University Hospital and Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany frank.buchholz@tu-dresden.de f.butter@imb-mainz.de dennis.kappei@nus.edu.sg.</nlm:affiliation><country wicri:rule="url">Allemagne</country><wicri:regionArea>Medical Systems Biology, UCC, University Hospital and Medical Faculty Carl Gustav Carus, TU Dresden, Dresden</wicri:regionArea><placeName><region type="land" nuts="1">Saxe (Land)</region><region type="district" nuts="2">District de Dresde</region><settlement type="city">Dresde</settlement></placeName></affiliation></author><author><name sortKey="Butter, Falk" sort="Butter, Falk" uniqKey="Butter F" first="Falk" last="Butter">Falk Butter</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Molecular Biology (IMB) gGmbH, Mainz, Germany frank.buchholz@tu-dresden.de f.butter@imb-mainz.de dennis.kappei@nus.edu.sg.</nlm:affiliation><country wicri:rule="url">Allemagne</country><wicri:regionArea>Institute of Molecular Biology (IMB) gGmbH, Mainz</wicri:regionArea><placeName><region type="land" nuts="2">Rhénanie-Palatinat</region><settlement type="city">Mayence</settlement></placeName></affiliation></author><author><name sortKey="Kappei, Dennis" sort="Kappei, Dennis" uniqKey="Kappei D" first="Dennis" last="Kappei">Dennis Kappei</name><affiliation wicri:level="4"><nlm:affiliation>Cancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore frank.buchholz@tu-dresden.de f.butter@imb-mainz.de dennis.kappei@nus.edu.sg.</nlm:affiliation><country wicri:rule="url">Allemagne</country><wicri:regionArea>Cancer Science Institute of Singapore, National University of Singapore, Singapore City</wicri:regionArea><wicri:noRegion>Singapore City</wicri:noRegion><orgName type="university">Université nationale de Singapour</orgName></affiliation></author></analytic><series><title level="j">EMBO reports</title><idno type="eISSN">1469-3178</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Telomeres constitute the ends of linear chromosomes and together with the shelterin complex form a structure essential for genome maintenance and stability. In addition to the constitutive binding of the shelterin complex, other direct, yet more transient interactions are mediated by the CST complex and HOT1/HMBOX1, while subtelomeric variant repeats are recognized by NR2C/F transcription factors. Recently, the Kruppel-like zinc finger protein ZBTB48/HKR3/TZAP has been described as a novel telomere-associated factor in the vertebrate lineage. Here, we show that ZBTB48 binds directly both to telomeric and to subtelomeric variant repeat sequences. ZBTB48 is found at telomeres of human cancer cells regardless of the mode of telomere maintenance and it acts as a negative regulator of telomere length. In addition to its telomeric function, we demonstrate through a combination of RNAseq, ChIPseq and expression proteomics experiments that ZBTB48 acts as a transcriptional activator on a small set of target genes, including mitochondrial fission process 1 (MTFP1). This discovery places ZBTB48 at the interface of telomere length regulation, transcriptional control and mitochondrial metabolism.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>France</li><li>Singapour</li></country><region><li>District de Dresde</li><li>Rhénanie-Palatinat</li><li>Saxe (Land)</li></region><settlement><li>Dresde</li><li>Mayence</li></settlement><orgName><li>Université nationale de Singapour</li></orgName></list><tree><country name="Allemagne"><region name="Saxe (Land)"><name sortKey="Jahn, Arne" sort="Jahn, Arne" uniqKey="Jahn A" first="Arne" last="Jahn">Arne Jahn</name></region><name sortKey="Bluhm, Alina" sort="Bluhm, Alina" uniqKey="Bluhm A" first="Alina" last="Bluhm">Alina Bluhm</name><name sortKey="Buchholz, Frank" sort="Buchholz, Frank" uniqKey="Buchholz F" first="Frank" last="Buchholz">Frank Buchholz</name><name sortKey="Butter, Falk" sort="Butter, Falk" uniqKey="Butter F" first="Falk" last="Butter">Falk Butter</name><name sortKey="Han, Chung Ting" sort="Han, Chung Ting" uniqKey="Han C" first="Chung-Ting" last="Han">Chung-Ting Han</name><name sortKey="Kappei, Dennis" sort="Kappei, Dennis" uniqKey="Kappei D" first="Dennis" last="Kappei">Dennis Kappei</name><name sortKey="Paszkowski Rogacz, Maciej" sort="Paszkowski Rogacz, Maciej" uniqKey="Paszkowski Rogacz M" first="Maciej" last="Paszkowski-Rogacz">Maciej Paszkowski-Rogacz</name><name sortKey="Sayols, Sergi" sort="Sayols, Sergi" uniqKey="Sayols S" first="Sergi" last="Sayols">Sergi Sayols</name></country><country name="Singapour"><noRegion><name sortKey="Rane, Grishma" sort="Rane, Grishma" uniqKey="Rane G" first="Grishma" last="Rane">Grishma Rane</name></noRegion><name sortKey="Kumar, Alan Prem" sort="Kumar, Alan Prem" uniqKey="Kumar A" first="Alan Prem" last="Kumar">Alan Prem Kumar</name></country><country name="France"><noRegion><name sortKey="Draskovi, Irena" sort="Draskovi, Irena" uniqKey="Draskovi I" first="Irena" last="Draškovi">Irena Draškovi</name></noRegion><name sortKey="Londo O Vallejo, Jose Arturo" sort="Londo O Vallejo, Jose Arturo" uniqKey="Londo O Vallejo J" first="José Arturo" last="Londo O-Vallejo">José Arturo Londo O-Vallejo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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