Mammalian transcription factor A is a core component of the mitochondrial transcription machinery
Artikel i vetenskaplig tidskrift, 2012

Transcription factor A (TFAM) functions as a DNA packaging factor in mammalian mitochondria. TFAM also binds sequence-specifically to sites immediately upstream of mitochondrial promoters, but there are conflicting data regarding its role as a core component of the mitochondrial transcription machinery. We here demonstrate that TFAM is required for transcription in mitochondrial extracts as well as in a reconstituted in vitro transcription system. The absolute requirement of TFAM can be relaxed by conditions that allow DNA breathing, i.e., low salt concentrations or negatively supercoiled DNA templates. The situation is thus very similar to that described in nuclear RNA polymerase II-dependent transcription, in which the free energy of supercoiling can circumvent the need for a subset of basal transcription factors at specific promoters. In agreement with these observations, we demonstrate that TFAM has the capacity to induce negative supercoils in DNA, and, using the recently developed nucleobase analog FRET-pair tC(O)-tC(nitro), we find that TFAM distorts significantly the DNA structure. Our findings differ from recent observations reporting that TFAM is not a core component of the mitochondrial transcription machinery. Instead, our findings support a model in which TFAM is absolutely required to recruit the transcription machinery during initiation of transcription.


Yonghong Shi

Göteborgs universitet

Anke Dierckx

Chalmers, Kemi- och bioteknik, Fysikalisk kemi

Paulina Wanrooij

Göteborgs universitet

Sjoerd Wanrooij

Göteborgs universitet

N. G. Larsson

Max Planck-institutet

Karolinska Institutet

Marcus Wilhelmsson

Chalmers, Kemi- och bioteknik, Fysikalisk kemi

Maria Falkenberg

Göteborgs universitet

Claes M Gustafsson

Göteborgs universitet

Proceedings of the National Academy of Sciences of the United States of America

0027-8424 (ISSN) 1091-6490 (eISSN)

Vol. 109 16510-16515


Nanovetenskap och nanoteknik

Livsvetenskaper och teknik


Fysikalisk kemi

Biokemi och molekylärbiologi