Mitochondrial transcription factor A, abbreviated as TFAM or mtTFA, is a protein that in humans is encoded by the TFAM gene.[5][6]
Function
This gene encodes a mitochondrial transcription factor that is a key activator of mitochondrial transcription and participates in mitochondrial genome replication. TFAM binds mitochondrial promoter DNA to aid transcription of the mitochondrial genome. Studies in mice have demonstrated that this gene product is required to regulate the mitochondrial genome copy number and is essential for embryonic development. A mouse model for Kearns–Sayre syndrome was produced when expression of this gene was eliminated by targeted disruption in heart and muscle cells.[6]
TFAM is a double box High-mobility group DNA-binding and bending protein.[7] This bending action is important for mitochondrial transcription initiation in mammals, but not in yeasts with the homolog Abf2. TFAM may also participate in the packaging of the mitochondrial genome, as its binding activity is non-sequence-specific. [8]
Interactions
TFAM has been shown to interact with TFB1M and[9] TFB2M.[10]
References
- GRCh38: Ensembl release 89: ENSG00000108064 – Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000003923 – Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- Tiranti V, Rossi E, Ruiz-Carrillo A, Rossi G, Rocchi M, DiDonato S, et al. (July 1995). "Chromosomal localization of mitochondrial transcription factor A (TCF6), single-stranded DNA-binding protein (SSBP), and endonuclease G (ENDOG), three human housekeeping genes involved in mitochondrial biogenesis". Genomics. 25 (2): 559–564. doi:10.1016/0888-7543(95)80058-T. PMID 7789991.
- "Entrez Gene: TFAM transcription factor A, mitochondrial". Archived from the original on 2010-12-05. Retrieved 2017-09-15.
- Murugesapillai D, McCauley MJ, Maher LJ, Williams MC (15 November 2016). "Single-molecule studies of high-mobility group B architectural DNA bending proteins". Biophysical Reviews. 9 (1): 17–40. doi:10.1007/s12551-016-0236-4. PMC 5331113. PMID 28303166.
- Ngo HB, Kaiser JT, Chan DC (October 2011). "The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA". Nature Structural & Molecular Biology. 18 (11): 1290–1296. doi:10.1038/nsmb.2159. PMC 3210390. PMID 22037171.
- McCulloch V, Shadel GS (August 2003). "Human mitochondrial transcription factor B1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activity". Molecular and Cellular Biology. 23 (16): 5816–5824. doi:10.1128/MCB.23.16.5816-5824.2003. PMC 166325. PMID 12897151.
- Hillen HS, Morozov YI, Sarfallah A, Temiakov D, Cramer P (November 2017). "Structural Basis of Mitochondrial Transcription Initiation". Cell. 171 (5): 1072–1081.e10. doi:10.1016/j.cell.2017.10.036. PMC 6590061. PMID 29149603.
Further reading
- Tominaga K, Akiyama S, Kagawa Y, Ohta S (1992). "Upstream region of a genomic gene for human mitochondrial transcription factor 1". Biochimica et Biophysica Acta. 1131 (2): 217–219. doi:10.1016/0167-4781(92)90082-b. PMID 1610904.
- Fisher RP, Lisowsky T, Parisi MA, Clayton DA (1992). "DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein". The Journal of Biological Chemistry. 267 (5): 3358–3367. doi:10.1016/S0021-9258(19)50739-6. PMID 1737790.
- Parisi MA, Clayton DA (1991). "Similarity of human mitochondrial transcription factor 1 to high mobility group proteins". Science. 252 (5008). New York, N.Y.: 965–969. Bibcode:1991Sci...252..965P. doi:10.1126/science.2035027. PMID 2035027.
- Tominaga K, Hayashi J, Kagawa Y, Ohta S (1993). "Smaller isoform of human mitochondrial transcription factor 1: its wide distribution and production by alternative splicing". Biochemical and Biophysical Research Communications. 194 (1): 544–551. doi:10.1006/bbrc.1993.1854. PMID 8333869.
- Larsson NG, Oldfors A, Garman JD, Barsh GS, Clayton DA (1997). "Down-regulation of mitochondrial transcription factor A during spermatogenesis in humans". Human Molecular Genetics. 6 (2): 185–191. doi:10.1093/hmg/6.2.185. PMID 9063738.
- Lezza AM, Pesce V, Cormio A, Fracasso F, Vecchiet J, Felzani G, et al. (2001). "Increased expression of mitochondrial transcription factor A and nuclear respiratory factor-1 in skeletal muscle from aged human subjects". FEBS Letters. 501 (1): 74–78. doi:10.1016/S0014-5793(01)02628-X. PMID 11457459. S2CID 45160010.
- Takamatsu C, Umeda S, Ohsato T, Ohno T, Abe Y, Fukuoh A, et al. (2002). "Regulation of mitochondrial D-loops by transcription factor A and single-stranded DNA-binding protein". EMBO Reports. 3 (5): 451–456. doi:10.1093/embo-reports/kvf099. PMC 1084112. PMID 11964388.
- Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM (2002). "Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA". Nature Genetics. 31 (3): 289–294. doi:10.1038/ng909. PMID 12068295. S2CID 11164308.
- Reyes A, Mezzina M, Gadaleta G (2002). "Human mitochondrial transcription factor A (mtTFA): gene structure and characterization of related pseudogenes". Gene. 291 (1–2): 223–232. doi:10.1016/S0378-1119(02)00600-5. PMID 12095695.
- Yoshida Y, Izumi H, Ise T, Uramoto H, Torigoe T, Ishiguchi H, et al. (2002). "Human mitochondrial transcription factor A binds preferentially to oxidatively damaged DNA". Biochemical and Biophysical Research Communications. 295 (4): 945–951. doi:10.1016/S0006-291X(02)00757-X. PMID 12127986.
- Garrido N, Griparic L, Jokitalo E, Wartiovaara J, van der Bliek AM, Spelbrink JN (2003). "Composition and dynamics of human mitochondrial nucleoids". Molecular Biology of the Cell. 14 (4): 1583–1596. doi:10.1091/mbc.E02-07-0399. PMC 153124. PMID 12686611.
- Yoshida Y, Izumi H, Torigoe T, Ishiguchi H, Itoh H, Kang D, et al. (2003). "P53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA". Cancer Research. 63 (13): 3729–3734. PMID 12839966.
- Deschauer M, Kiefer R, Blakely EL, He L, Zierz S, Turnbull DM, et al. (2003). "A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia". Neuromuscular Disorders. 13 (7–8): 568–572. doi:10.1016/S0960-8966(03)00071-3. PMID 12921794. S2CID 23020569.
- Günther C, von Hadeln K, Müller-Thomsen T, Alberici A, Binetti G, Hock C, et al. (2005). "Possible association of mitochondrial transcription factor A (TFAM) genotype with sporadic Alzheimer disease". Neuroscience Letters. 369 (3): 219–223. doi:10.1016/j.neulet.2004.07.070. PMID 15464268. S2CID 25710306.
- Kanki T, Ohgaki K, Gaspari M, Gustafsson CM, Fukuoh A, Sasaki N, et al. (2004). "Architectural role of mitochondrial transcription factor A in maintenance of human mitochondrial DNA". Molecular and Cellular Biology. 24 (22): 9823–9834. doi:10.1128/MCB.24.22.9823-9834.2004. PMC 525493. PMID 15509786.
- Cam H, Balciunaite E, Blais A, Spektor A, Scarpulla RC, Young R, et al. (2004). "A common set of gene regulatory networks links metabolism and growth inhibition". Molecular Cell. 16 (3): 399–411. doi:10.1016/j.molcel.2004.09.037. PMID 15525513.