Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/149068
Title: | DNA specificities modulate the binding of human transcription factor A to mitochondrial DNA control region |
Author: | Cuppari, Anna Fernández Millán, Pablo Battistini, Federica Tarrés Solé, Aleix Lyonnais, Sébastien Iruela Martín, Guillermo Ruiz López, Elena Enciso, Yuliana Rubio Cosials, Anna Prohens López, Rafael Pons Vallès, Miquel Alfonso, Carlos Tóth, Katalin Rivas, Germán Orozco López, Modesto Solà Vilarrubias, Maria |
Keywords: | ADN mitocondrial Transcripció genètica Mitochondrial DNA Genetic transcription |
Issue Date: | 22-May-2019 |
Publisher: | Oxford University Press |
Abstract: | Human mitochondrial DNA (h-mtDNA) codes for 13 subunits of the oxidative phosphorylation pathway, the essential route that produces ATP. H-mtDNA transcription and replication depends on the transcription factor TFAM, which also maintains and compacts this genome. It is well-established that TFAM activates the mtDNA promoters LSP and HSP1 at the mtDNA control region where DNA regulatory elements cluster. Previous studies identified still uncharacterized, additional binding sites at the control region downstream from and slightly similar to LSP, namely sequences X and Y (Site-X and Site-Y) (Fisher et al., Cell 50, pp 247-258, 1987). Here, we explore TFAM binding at these two sites and compare them to LSP by multiple experimental and in silico methods. Our results show that TFAM binding is strongly modulated by the sequence-dependent properties of Site-X, Site-Y and LSP. The high binding versatility of Site-Y or the considerable stiffness of Site-X tune TFAM interactions. In addition, we show that increase in TFAM/DNA complex concentration induces multimerization, which at a very high concentration triggers disruption of preformed complexes. Therefore, our results suggest that mtDNA sequences induce non-uniform TFAM binding and, consequently, direct an uneven distribution of TFAM aggregation sites during the essential process of mtDNA compaction |
Note: | Reproducció del document publicat a: https://doi.org/10.1093/nar/gkz406 |
It is part of: | Nucleic Acids Research, 2019, vol. 47, num. 12, p. 6519-6537 |
URI: | http://hdl.handle.net/2445/149068 |
Related resource: | https://doi.org/10.1093/nar/gkz406 |
ISSN: | 0305-1048 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Química Inorgànica i Orgànica) Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
690202.pdf | 6.59 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License