| Autor: |
Dostal, Vishantie, Churchill, Mair E.A. |
| Zdroj: |
BBA - Gene Regulatory Mechanisms; May2019, Vol. 1862 Issue 5, p598-607, 10p |
| Abstrakt: |
Abstract In eukaryotes, cytosine methylation of nuclear DNA at CpG sequences (5mCpG) regulates epigenetic inheritance through alterations in chromatin structure. However, mitochondria lack nucleosomal chromatin, therefore the molecular mechanisms by which 5mCpG influences mitochondria must be different and are as yet unknown. Mitochondrial Transcription Factor A (TFAM) is both the primary DNA-compacting protein in the mitochondrial DNA (mtDNA) nucleoid and a transcription-initiation factor. TFAM must encounter hundreds of CpGs in mtDNA, so the occurrence of 5mCpG has the potential to impact TFAM-DNA recognition. We used biophysical approaches to determine whether 5mCpG alters any TFAM-dependent activities. 5mCpG in the heavy strand promoter (HSP1) increased the binding affinity of TFAM and induced TFAM multimerization with increased cooperativity compared to nonmethylated DNA. However, 5mCpG had no apparent effect on TFAM-dependent DNA compaction. Additionally, 5mCpG had a clear and context-dependent effect on transcription initiating from the three mitochondrial promoters. Taken together, our findings demonstrate that 5mCpG in the mitochondrial promoter region does impact TFAM-dependent activities in vitro. Highlights • Methylation of specific mitochondrial DNA increases the binding affinity of TFAM. • Multimerization of TFAM on site-specific promoter DNA is enhanced by methylation. • Effect of DNA methylation on transcription initiation is promoter context dependent. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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