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Genome methylation in D. melanogaster is found at specific short motifs and is independent of DNMT2 activity

Takayama, Sachiko and Dhahbi, Joseph and Roberts, Adam and Mao, Guanxiong and Heo, Seok-Jin and Pachter, Lior and Martin, David I. K. and Boffelli, Dario (2014) Genome methylation in D. melanogaster is found at specific short motifs and is independent of DNMT2 activity. Genome Research, 24 (5). pp. 821-830. ISSN 1088-9051. PMCID PMC4009611. https://resolver.caltech.edu/CaltechAUTHORS:20170303-142644662

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Abstract

Cytosine methylation in the genome of Drosophila melanogaster has been elusive and controversial: Its location and function have not been established. We have used a novel and highly sensitive genomewide cytosine methylation assay to detect and map genome methylation in stage 5 Drosophila embryos. The methylation we observe with this method is highly localized and strand asymmetrical, limited to regions covering ∼1% of the genome, dynamic in early embryogenesis, and concentrated in specific 5-base sequence motifs that are CA- and CT-rich but depleted of guanine. Gene body methylation is associated with lower expression, and many genes containing methylated regions have developmental or transcriptional functions. The only known DNA methyltransferase in Drosophila is the DNMT2 homolog MT2, but lines deficient for MT2 retain genomic methylation, implying the presence of a novel methyltransferase. The association of methylation with a lower expression of specific developmental genes at stage 5 raises the possibility that it participates in controlling gene expression during the maternal-zygotic transition.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1101/gr.162412.113DOIArticle
http://genome.cshlp.org/content/24/5/821PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009611/PubMed CentralArticle
http://genome.cshlp.org/content/24/5/821/suppl/DC1PublisherSupplemental Material
Additional Information:© 2014 Takayama et al. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. Received June 21, 2013. Accepted February 18, 2014. We thank Mark Biggin and Xiaoyong Li for the Canton-S Drosophila melanogaster DNA; Gunther Reuter and Frank Lyko for the Mt2 mutant strains and DNA; Sarah Siegrist for fly stocks, husbandry and other resources, and technical help and discussions. This work was supported by the NIH grants HL084474 (D.B.), ES016581 (D.I.K.M.), CA115768 (D.I.K.M.). J.D. was a Scholar of the California Institute of Regenerative Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author contributions: D.I.K.M. conceived the study; J.D. designed and performed the MeDIP-bisulfite deep sequencing experiments; S.T. performed the fly husbandry, obtained unfertilized oocytes, and carried out bisulfite PCR experiments; S.J.H. constructed the bisulfite-PCR sequencing libraries; S.T., G.M., and D.B. designed and performed bioinformatic analyses; A.R. and L.P. carried out the association between methylation and gene expression; D.I.K.M. and D.B. wrote the paper. Data access: Sequencing data from this study have been submitted to the NCBI Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/) under accession number GSE34425. Bisulfite sequencing data have been submitted to the NCBI Sequence Read Archive (SRA; http://www.ncbi.nlm.nih.gov/sra) under accession nos. SRR1191286, SRR1191445, SRR1191486, SRR1191487, SRR1191684, and SRR1191728.
Funders:
Funding AgencyGrant Number
NIHHL084474
NIHES016581
NIHCA115768
California Institute of Regenerative MedicineUNSPECIFIED
Issue or Number:5
PubMed Central ID:PMC4009611
Record Number:CaltechAUTHORS:20170303-142644662
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170303-142644662
Official Citation:Genome methylation in D. melanogaster is found at specific short motifs and is independent of DNMT2 activity Sachiko Takayama, Joseph Dhahbi, Adam Roberts, Guanxiong Mao, Seok-Jin Heo, Lior Pachter, David I.K. Martin, and Dario Boffelli Genome Res. May 2014 24: 821-830; Published in Advance February 20, 2014, doi:10.1101/gr.162412.113
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74716
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:04 Mar 2017 00:05
Last Modified:03 Oct 2019 16:42

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