PMID- 32461362
OWN - NLM
STAT- MEDLINE
DCOM- 20200821
LR  - 20240426
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 117
IP  - 23
DP  - 2020 Jun 9
TI  - Adenine DNA methylation, 3D genome organization, and gene expression in the 
      parasite Trichomonas vaginalis.
PG  - 13033-13043
LID - 10.1073/pnas.1917286117 [doi]
AB  - Trichomonas vaginalis is a common sexually transmitted parasite that colonizes 
      the human urogenital tract causing infections that range from asymptomatic to 
      highly inflammatory. Recent works have highlighted the importance of histone 
      modifications in the regulation of transcription and parasite pathogenesis. 
      However, the nature of DNA methylation in the parasite remains unexplored. Using 
      a combination of immunological techniques and ultrahigh-performance liquid 
      chromatography (UHPLC), we analyzed the abundance of DNA methylation in strains 
      with differential pathogenicity demonstrating that N6-methyladenine (6mA), and 
      not 5-methylcytosine (5mC), is the main DNA methylation mark in T. vaginalis 
      Genome-wide distribution of 6mA reveals that this mark is enriched at intergenic 
      regions, with a preference for certain superfamilies of DNA transposable 
      elements. We show that 6mA in T. vaginalis is associated with silencing when 
      present on genes. Interestingly, bioinformatics analysis revealed the presence of 
      transcriptionally active or repressive intervals flanked by 6mA-enriched regions, 
      and results from chromatin conformation capture (3C) experiments suggest these 
      6mA flanked regions are in close spatial proximity. These associations were 
      disrupted when parasites were treated with the demethylation activator ascorbic 
      acid. This finding revealed a role for 6mA in modulating three-dimensional (3D) 
      chromatin structure and gene expression in this divergent member of the Excavata.
FAU - Lizarraga, Ayelen
AU  - Lizarraga A
AD  - Laboratorio de Parasitos Anaerobios, Instituto Tecnologico Chascomus, National 
      Scientific and Technical Research Council-National University of San Martin 
      (CONICET-UNSAM), B7130IWA Chascomus, Argentina.
FAU - O'Brown, Zach Klapholz
AU  - O'Brown ZK
AD  - Division of Newborn Medicine, Children's Hospital Boston, Boston, MA 02115.
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
FAU - Boulias, Konstantinos
AU  - Boulias K
AD  - Division of Newborn Medicine, Children's Hospital Boston, Boston, MA 02115.
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
FAU - Roach, Lara
AU  - Roach L
AUID- ORCID: 0000-0003-2534-6588
AD  - Division of Newborn Medicine, Children's Hospital Boston, Boston, MA 02115.
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
FAU - Greer, Eric Lieberman
AU  - Greer EL
AUID- ORCID: 0000-0002-7501-7371
AD  - Division of Newborn Medicine, Children's Hospital Boston, Boston, MA 02115.
AD  - Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
FAU - Johnson, Patricia J
AU  - Johnson PJ
AD  - Department of Microbiology, Immunology & Molecular Genetics, University of 
      California, Los Angeles, CA 90095; johnsonp@ucla.edu ndemiguel@intech.gov.ar.
FAU - Strobl-Mazzulla, Pablo H
AU  - Strobl-Mazzulla PH
AUID- ORCID: 0000-0003-0591-6168
AD  - Laboratorio de Biologia del Desarrollo, Instituto Tecnologico Chascomus, 
      CONICET-UNSAM, B7130IWA Chascomus, Argentina.
FAU - de Miguel, Natalia
AU  - de Miguel N
AUID- ORCID: 0000-0002-3864-0703
AD  - Laboratorio de Parasitos Anaerobios, Instituto Tecnologico Chascomus, National 
      Scientific and Technical Research Council-National University of San Martin 
      (CONICET-UNSAM), B7130IWA Chascomus, Argentina; johnsonp@ucla.edu 
      ndemiguel@intech.gov.ar.
LA  - eng
GR  - DP2 AG055947/AG/NIA NIH HHS/United States
GR  - R01 AI030537/AI/NIAID NIH HHS/United States
GR  - R21 HG010066/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200527
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Chromatin)
RN  - 0 (DNA Transposable Elements)
RN  - JAC85A2161 (Adenine)
RN  - PQ6CK8PD0R (Ascorbic Acid)
SB  - IM
MH  - Adenine/*metabolism
MH  - Ascorbic Acid/pharmacology
MH  - Cell Culture Techniques
MH  - Chromatin/*chemistry/genetics/metabolism
MH  - Computational Biology
MH  - DNA Methylation/drug effects/*genetics
MH  - DNA Transposable Elements/genetics
MH  - Gene Expression Regulation
MH  - High-Throughput Nucleotide Sequencing
MH  - Molecular Conformation
MH  - Sequence Analysis, DNA
MH  - Trichomonas vaginalis/*genetics
PMC - PMC7293704
OTO - NOTNLM
OT  - Trichomonas
OT  - adenine methylation
OT  - gene expression
COIS- The authors declare no competing interest.
EDAT- 2020/05/29 06:00
MHDA- 2020/08/22 06:00
PMCR- 2020/11/27
CRDT- 2020/05/29 06:00
PHST- 2020/05/29 06:00 [pubmed]
PHST- 2020/08/22 06:00 [medline]
PHST- 2020/05/29 06:00 [entrez]
PHST- 2020/11/27 00:00 [pmc-release]
AID - 1917286117 [pii]
AID - 201917286 [pii]
AID - 10.1073/pnas.1917286117 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2020 Jun 9;117(23):13033-13043. doi: 
      10.1073/pnas.1917286117. Epub 2020 May 27.