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Title: Widespread adenine N6-methylation of active genes in fungi

Abstract

N6-methyldeoxyadenine (6mA) is a noncanonical DNA base modification present at low levels in plant and animal genomes, but its prevalence and association with genome function in other eukaryotic lineages remains poorly understood. We report that abundant 6mA is associated with transcriptionally active genes in early-diverging fungal lineages. Using single-molecule long-read sequencing of 16 diverse fungal genomes, we observed that up to 2.8% of all adenines were methylated in early-diverging fungi, far exceeding levels observed in other eukaryotes and more derived fungi. 6mA occurred symmetrically at ApT dinucleotides and was concentrated in dense methylated adenine clusters surrounding the transcriptional start sites of expressed genes; its distribution was inversely correlated with that of 5-methylcytosine. Our results show a striking contrast in the genomic distributions of 6mA and 5-methylcytosine and reinforce a distinct role for 6mA as a gene-expression-associated epigenomic mark in eukaryotes.

Authors:
 [1];  [2];  [1];  [1];  [3];  [1];  [1];  [1];  [1];  [4];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [5] more »;  [3];  [6];  [7];  [7];  [8];  [9]; ORCiD logo [10];  [11]; ORCiD logo [12];  [4] « less
  1. USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)
  2. USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Roche Sequencing Solutions Inc., Pleasanton, CA (United States)
  3. Univ. of Georgia, Athens, GA (United States). Dept. of Genetics
  4. USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology
  5. USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); The Jackson Lab. for Genomic Medicine, Farmington, CT (United States)
  6. L. F. Lambert Spawn Co., Coatesville, PA (United States)
  7. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  8. Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Ecology and Evolutionary Biology
  9. Univ. of California, Santa Barbara, CA (United States). Dept. of Chemical Engineering
  10. Univ. of California, Riverside, CA (United States). Dept. of Plant Pathology and Microbiology
  11. Oregon State Univ., Corvallis, OR (United States). Dept. of Botany and Plant Pathology
  12. USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Univ. of California, Merced, CA (United States). School of Natural Sciences
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Santa Barbara, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Scientific User Facilities Division; National Science Foundation (NSF); Pew Charitable Trusts
OSTI Identifier:
1469129
Alternate Identifier(s):
OSTI ID: 1485164
Grant/Contract Number:  
AC02-05CH11231; DEB-1441715; DEB-1441604; DEB-1354625; SC0010352; W911NF-09- 0001
Resource Type:
Accepted Manuscript
Journal Name:
Nature Genetics
Additional Journal Information:
Journal Volume: 49; Journal Issue: 6; Related Information: © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.; Journal ID: ISSN 1061-4036
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Mondo, Stephen J., Dannebaum, Richard O., Kuo, Rita C., Louie, Katherine B., Bewick, Adam J., LaButti, Kurt, Haridas, Sajeet, Kuo, Alan, Salamov, Asaf, Ahrendt, Steven R., Lau, Rebecca, Bowen, Benjamin P., Lipzen, Anna, Sullivan, William, Andreopoulos, Bill B., Clum, Alicia, Lindquist, Erika, Daum, Christopher, Northen, Trent R., Kunde-Ramamoorthy, Govindarajan, Schmitz, Robert J., Gryganskyi, Andrii, Culley, David, Magnuson, Jon, James, Timothy Y., O'Malley, Michelle A., Stajich, Jason E., Spatafora, Joseph W., Visel, Axel, and Grigoriev, Igor V. Widespread adenine N6-methylation of active genes in fungi. United States: N. p., 2017. Web. doi:10.1038/ng.3859.
Mondo, Stephen J., Dannebaum, Richard O., Kuo, Rita C., Louie, Katherine B., Bewick, Adam J., LaButti, Kurt, Haridas, Sajeet, Kuo, Alan, Salamov, Asaf, Ahrendt, Steven R., Lau, Rebecca, Bowen, Benjamin P., Lipzen, Anna, Sullivan, William, Andreopoulos, Bill B., Clum, Alicia, Lindquist, Erika, Daum, Christopher, Northen, Trent R., Kunde-Ramamoorthy, Govindarajan, Schmitz, Robert J., Gryganskyi, Andrii, Culley, David, Magnuson, Jon, James, Timothy Y., O'Malley, Michelle A., Stajich, Jason E., Spatafora, Joseph W., Visel, Axel, & Grigoriev, Igor V. Widespread adenine N6-methylation of active genes in fungi. United States. doi:10.1038/ng.3859.
Mondo, Stephen J., Dannebaum, Richard O., Kuo, Rita C., Louie, Katherine B., Bewick, Adam J., LaButti, Kurt, Haridas, Sajeet, Kuo, Alan, Salamov, Asaf, Ahrendt, Steven R., Lau, Rebecca, Bowen, Benjamin P., Lipzen, Anna, Sullivan, William, Andreopoulos, Bill B., Clum, Alicia, Lindquist, Erika, Daum, Christopher, Northen, Trent R., Kunde-Ramamoorthy, Govindarajan, Schmitz, Robert J., Gryganskyi, Andrii, Culley, David, Magnuson, Jon, James, Timothy Y., O'Malley, Michelle A., Stajich, Jason E., Spatafora, Joseph W., Visel, Axel, and Grigoriev, Igor V. Mon . "Widespread adenine N6-methylation of active genes in fungi". United States. doi:10.1038/ng.3859. https://www.osti.gov/servlets/purl/1469129.
@article{osti_1469129,
title = {Widespread adenine N6-methylation of active genes in fungi},
author = {Mondo, Stephen J. and Dannebaum, Richard O. and Kuo, Rita C. and Louie, Katherine B. and Bewick, Adam J. and LaButti, Kurt and Haridas, Sajeet and Kuo, Alan and Salamov, Asaf and Ahrendt, Steven R. and Lau, Rebecca and Bowen, Benjamin P. and Lipzen, Anna and Sullivan, William and Andreopoulos, Bill B. and Clum, Alicia and Lindquist, Erika and Daum, Christopher and Northen, Trent R. and Kunde-Ramamoorthy, Govindarajan and Schmitz, Robert J. and Gryganskyi, Andrii and Culley, David and Magnuson, Jon and James, Timothy Y. and O'Malley, Michelle A. and Stajich, Jason E. and Spatafora, Joseph W. and Visel, Axel and Grigoriev, Igor V.},
abstractNote = {N6-methyldeoxyadenine (6mA) is a noncanonical DNA base modification present at low levels in plant and animal genomes, but its prevalence and association with genome function in other eukaryotic lineages remains poorly understood. We report that abundant 6mA is associated with transcriptionally active genes in early-diverging fungal lineages. Using single-molecule long-read sequencing of 16 diverse fungal genomes, we observed that up to 2.8% of all adenines were methylated in early-diverging fungi, far exceeding levels observed in other eukaryotes and more derived fungi. 6mA occurred symmetrically at ApT dinucleotides and was concentrated in dense methylated adenine clusters surrounding the transcriptional start sites of expressed genes; its distribution was inversely correlated with that of 5-methylcytosine. Our results show a striking contrast in the genomic distributions of 6mA and 5-methylcytosine and reinforce a distinct role for 6mA as a gene-expression-associated epigenomic mark in eukaryotes.},
doi = {10.1038/ng.3859},
journal = {Nature Genetics},
number = 6,
volume = 49,
place = {United States},
year = {2017},
month = {5}
}

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Figures / Tables:

Figure 1 Figure 1: Phylogenetic diversity of genomes sequenced in this study and associated 6mA features. (a) RAxML (ref. 20) maximum-likelihood phylogeny constructed including 285 single-copy genes from all lineages sequenced in this study and four references in which 6mA has been analyzed previously. Node ages indicate date of divergence, from ref.more » 5. Clades are colored at phylum, class and subphylum levels; bootstrap support for all nodes is 100 unless otherwise noted (shown in black at branches). Mya, million years ago; Bya, billion years ago. (b) Percent of total adenines methylated across all surveyed fungi plus outgroups. For additional data on cytosine methylation, see Supplementary Figure 8. ID abbreviations were generated for each lineage based on the first letter of the genus and first one or two letters of the species. (c) Methylation marks in early-diverging fungi are symmetric at ApT sites. The x axis shows the frequency of ApT methylation compared to any other adenine-containing dinucleotide (AV) combination. Although impacted by GC content, the frequency of ApT methylation by chance is expected to be around 25%. Colors and names of lineage groups as in b. (d) Percent of total 6mA marks found within MACs. No MACs were found in R. globosum or L. creatinivora.« less

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