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A/T Run Geometry of B-form DNA Is Independent of Bound Methyl-CpG Binding Domain, Cytosine Methylation and Flanking Sequence.

Chia JY, Tan WS, Ng CL, Hu NJ, Foo HL, Ho KL
Sci Rep 6 31210 (2016)
Cited: 7 times
EuropePMC logo PMID: 27502833

Abstract

DNA methylation in a CpG context can be recognised by methyl-CpG binding protein 2 (MeCP2) via its methyl-CpG binding domain (MBD). An A/T run next to a methyl-CpG maximises the binding of MeCP2 to the methylated DNA. The A/T run characteristics are reported here with an X-ray structure of MBD A140V in complex with methylated DNA. The A/T run geometry was found to be strongly stabilised by a string of conserved water molecules regardless of its flanking nucleotide sequences, DNA methylation and bound MBD. New water molecules were found to stabilise the Rett syndrome-related E137, whose carboxylate group is salt bridged to R133. A structural comparison showed no difference between the wild type and MBD A140V. However, differential scanning calorimetry showed that the melting temperature of A140V constructs in complex with methylated DNA was reduced by ~7 °C, although circular dichroism showed no changes in the secondary structure content for A140V. A band shift analysis demonstrated that the larger fragment of MeCP2 (A140V) containing the transcriptional repression domain (TRD) destabilises the DNA binding. These results suggest that the solution structure of MBD A140V may differ from the wild-type MBD although no changes in the biochemical properties of X-ray A140V were observed.

Reviews - 5bt2 mentioned but not cited (1)

  1. MeCP2: The Genetic Driver of Rett Syndrome Epigenetics. Good KV, Vincent JB, Ausió J. Front Genet 12 620859 (2021)

Articles - 5bt2 mentioned but not cited (5)

  1. Cytosine methylation of mitochondrial DNA at CpG sequences impacts transcription factor A DNA binding and transcription. Dostal V, Churchill MEA. Biochim Biophys Acta Gene Regul Mech 1862 598-607 (2019)
  2. A/T Run Geometry of B-form DNA Is Independent of Bound Methyl-CpG Binding Domain, Cytosine Methylation and Flanking Sequence. Chia JY, Tan WS, Ng CL, Hu NJ, Foo HL, Ho KL. Sci Rep 6 31210 (2016)
  3. Structural investigation of Rett-inducing MeCP2 mutations. Spiga O, Gardini S, Rossi N, Cicaloni V, Pettini F, Niccolai N, Santucci A. Genes Dis 6 31-34 (2019)
  4. In silico prediction and interaction of resveratrol on methyl-CpG binding proteins by molecular docking and MD simulations study. Sahu RK, Verma VV, Kumar A, Tandon S, Chandra Das B, Hedau ST. RSC Adv 12 11493-11504 (2022)
  5. An early seizure variant type of a male Rett syndrome patient with a MECP2 p.Arg133His missense mutation. Yoon JA, Yoo Y, Lee JS, Kim YM, Shin YB. Mol Genet Genomic Med 7 e532 (2019)


Articles citing this publication (1)

  1. Structural Basis of MeCP2 Distribution on Non-CpG Methylated and Hydroxymethylated DNA. Sperlazza MJ, Bilinovich SM, Sinanan LM, Javier FR, Williams DC. J Mol Biol 429 1581-1594 (2017)


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