Specificity of the ModA11, ModA12 and ModD1 epigenetic regulator N-6-adenine DNA methyltransferases of Neisseria meningitidis

Seib, Kate L and Jen, Freda EC and Tan, Aimee and Scott, Adeana L and Kumar, Ritesh and Power, Peter M and Chen, Li-Tzu and Wu, Hsing-Ju and Wang, Andrew HJ and Hill, Dorothea MC and Luyten, Yvette A and Morgan, Richard D and Roberts, Richard J and Maiden, Martin CJ and Boitano, Matthew and Clark, Tyson A and Korlach, Jonas and Rao, Desirazu N and Jennings, Michael P (2015) Specificity of the ModA11, ModA12 and ModD1 epigenetic regulator N-6-adenine DNA methyltransferases of Neisseria meningitidis. In: NUCLEIC ACIDS RESEARCH, 43 (8). pp. 4150-4162.

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Abstract

Phase variation (random ON/OFF switching) of gene expression is a common feature of host-adapted pathogenic bacteria. Phase variably expressed N-6-adenine DNA methyltransferases (Mod) alter global methylation patterns resulting in changes in gene expression. These systems constitute phase variable regulons called phasevarions. Neisseria meningitidis phasevarions regulate genes including virulence factors and vaccine candidates, and alter phenotypes including antibiotic resistance. The target site recognized by these Type III N-6-adenine DNA methyltransferases is not known. Single molecule, real-time (SMRT) methylome analysis was used to identify the recognition site for three key N. meningitidis methyltransferases: ModA11 (exemplified by M.NmeMC58I) (5'-CGY(m6)AG-3'), ModA12 (exemplified by M.Nme77I, M.Nme18I and M.Nme579II) (5'-AC(m6)ACC-3') and ModD1 (exemplified by M.Nme579I) (5'-CC(m6)AGC-3'). Restriction inhibition assays and mutagenesis confirmed the SMRT methylome analysis. The ModA11 site is complex and atypical and is dependent on the type of pyrimidine at the central position, in combination with the bases flanking the core recognition sequence 5'-CGY(m6)AG-3'. The observed efficiency of methylation in the modA11 strain (MC58) genome ranged from 4.6% at 5'-GCGC(m6)AGG-3' sites, to 100% at 5'-ACGT(m6)AGG-3' sites. Analysis of the distribution of modified sites in the respective genomes shows many cases of association with intergenic regions of genes with altered expression due to phasevarion switching.

Item Type:	Journal Article
Publication:	NUCLEIC ACIDS RESEARCH
Publisher:	OXFORD UNIV PRESS
Additional Information:	Copy right for this article belongs to the OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	26 Jun 2015 07:29
Last Modified:	26 Jun 2015 07:29
URI:	http://eprints.iisc.ac.in/id/eprint/51781

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