TFAM explained

Mitochondrial transcription factor A, abbreviated as TFAM or mtTFA, is a protein that in humans is encoded by the TFAM gene.^{[1] [2]}

Function

This gene encodes a mitochondrial transcription factor that is a key activator of mitochondrial transcription as well as a participant 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.

TFAM is a double box High-mobility group DNA-binding and bending protein.^[3] 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. ^[4]

Interactions

TFAM has been shown to interact with TFB1M and^[5] TFB2M.^[6]

Further reading

• Tominaga K, Akiyama S, Kagawa Y, Ohta S . Upstream region of a genomic gene for human mitochondrial transcription factor 1. . Biochim. Biophys. Acta . 1131 . 2 . 217–9 . 1992 . 1610904 . 10.1016/0167-4781(92)90082-b .
• Fisher RP, Lisowsky T, Parisi MA, Clayton DA . DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein. . J. Biol. Chem. . 267 . 5 . 3358–67 . 1992 . 10.1016/S0021-9258(19)50739-6 . 1737790 . free .
• Parisi MA, Clayton DA . Similarity of human mitochondrial transcription factor 1 to high mobility group proteins. . Science . 252 . 5008 . 965–9 . 1991 . 2035027 . 10.1126/science.2035027 . 1991Sci...252..965P .
• Tominaga K, Hayashi J, Kagawa Y, Ohta S . Smaller isoform of human mitochondrial transcription factor 1: its wide distribution and production by alternative splicing. . Biochem. Biophys. Res. Commun. . 194 . 1 . 544–51 . 1993 . 8333869 . 10.1006/bbrc.1993.1854 .
• Larsson NG, Oldfors A, Garman JD, Barsh GS, Clayton DA . Down-regulation of mitochondrial transcription factor A during spermatogenesis in humans. . Hum. Mol. Genet. . 6 . 2 . 185–91 . 1997 . 9063738 . 10.1093/hmg/6.2.185 . free .
• Lezza AM, Pesce V, Cormio A, Fracasso F, Vecchiet J, Felzani G, Cantatore P, Gadaleta MN . Increased expression of mitochondrial transcription factor A and nuclear respiratory factor-1 in skeletal muscle from aged human subjects. . FEBS Lett. . 501 . 1 . 74–8 . 2001 . 11457459 . 10.1016/S0014-5793(01)02628-X . 45160010 . free .
• Takamatsu C, Umeda S, Ohsato T, Ohno T, Abe Y, Fukuoh A, Shinagawa H, Hamasaki N, Kang D . Regulation of mitochondrial D-loops by transcription factor A and single-stranded DNA-binding protein. . EMBO Rep. . 3 . 5 . 451–6 . 2002 . 11964388 . 1084112 . 10.1093/embo-reports/kvf099 .
• Maria Falkenberg. Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM . Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA. . Nat. Genet. . 31 . 3 . 289–94 . 2002 . 12068295 . 10.1038/ng909 . 11164308 .
• Reyes A, Mezzina M, Gadaleta G . Human mitochondrial transcription factor A (mtTFA): gene structure and characterization of related pseudogenes. . Gene . 291 . 1–2 . 223–32 . 2002 . 12095695 . 10.1016/S0378-1119(02)00600-5 .
• Yoshida Y, Izumi H, Ise T, Uramoto H, Torigoe T, Ishiguchi H, Murakami T, Tanabe M, Nakayama Y, Itoh H, Kasai H, Kohno K . Human mitochondrial transcription factor A binds preferentially to oxidatively damaged DNA. . Biochem. Biophys. Res. Commun. . 295 . 4 . 945–51 . 2002 . 12127986 . 10.1016/S0006-291X(02)00757-X .
• Garrido N, Griparic L, Jokitalo E, Wartiovaara J, van der Bliek AM, Spelbrink JN . Composition and dynamics of human mitochondrial nucleoids. . Mol. Biol. Cell . 14 . 4 . 1583–96 . 2003 . 12686611 . 153124 . 10.1091/mbc.E02-07-0399 .
• Yoshida Y, Izumi H, Torigoe T, Ishiguchi H, Itoh H, Kang D, Kohno K . P53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA. . Cancer Res. . 63 . 13 . 3729–34 . 2003 . 12839966 .
• McCulloch V, Shadel GS . Human mitochondrial transcription factor B1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activity. . Mol. Cell. Biol. . 23 . 16 . 5816–24 . 2003 . 12897151 . 166325 . 10.1128/MCB.23.16.5816-5824.2003 .
• Deschauer M, Kiefer R, Blakely EL, He L, Zierz S, Turnbull DM, Taylor RW . A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia. . Neuromuscul. Disord. . 13 . 7–8 . 568–72 . 2003 . 12921794 . 10.1016/S0960-8966(03)00071-3 . 23020569 .
• Günther C, von Hadeln K, Müller-Thomsen T, Alberici A, Binetti G, Hock C, Nitsch RM, Stoppe G, Reiss J, Gal A, Finckh U . Possible association of mitochondrial transcription factor A (TFAM) genotype with sporadic Alzheimer disease. . Neurosci. Lett. . 369 . 3 . 219–23 . 2005 . 15464268 . 10.1016/j.neulet.2004.07.070 . 25710306 .
• Kanki T, Ohgaki K, Gaspari M, Gustafsson CM, Fukuoh A, Sasaki N, Hamasaki N, Kang D . Architectural role of mitochondrial transcription factor A in maintenance of human mitochondrial DNA. . Mol. Cell. Biol. . 24 . 22 . 9823–34 . 2004 . 15509786 . 525493 . 10.1128/MCB.24.22.9823-9834.2004 .
• Cam H, Balciunaite E, Blais A, Spektor A, Scarpulla RC, Young R, Kluger Y, Dynlacht BD . A common set of gene regulatory networks links metabolism and growth inhibition. . Mol. Cell . 16 . 3 . 399–411 . 2004 . 15525513 . 10.1016/j.molcel.2004.09.037 . free .

Notes and References

1. Tiranti V, Rossi E, Ruiz-Carrillo A, Rossi G, Rocchi M, DiDonato S, Zuffardi O, Zeviani M . 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 . 559–64 . Jul 1995 . 7789991 . 10.1016/0888-7543(95)80058-T .
2. Web site: Entrez Gene: TFAM transcription factor A, mitochondrial.
3. Murugesapillai D, McCauley MJ, Maher LJ, Williams MC . Single-molecule studies of high-mobility group B architectural DNA bending proteins . Biophysical Reviews . 15 November 2016 . 10.1007/s12551-016-0236-4 . 5331113 . 28303166 . 9 . 1 . 17–40.
4. Ngo . HB . Kaiser . JT . Chan . DC . The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA. . Nature Structural & Molecular Biology . 30 October 2011 . 18 . 11 . 1290–6 . 10.1038/nsmb.2159 . 22037171 . 3210390.
5. McCulloch V, Shadel GS . Human mitochondrial transcription factor B1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activity . Mol. Cell. Biol. . 23 . 16 . 5816–24 . Aug 2003 . 12897151 . 166325 . 10.1128/MCB.23.16.5816-5824.2003 .
6. Hillen . HS . Morozov . YI . Sarfallah . A . Temiakov . D . Cramer . P . Structural Basis of Mitochondrial Transcription Initiation. . Cell . 16 November 2017 . 171 . 5 . 1072–1081.e10 . 10.1016/j.cell.2017.10.036 . 29149603. 6590061 .