A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment.
Adenosine Triphosphatases
/ chemistry
Animals
Cats
Chromatin
Fibroblasts
/ parasitology
Histone Code
Histone Deacetylases
/ chemistry
Histones
/ genetics
Humans
Life Cycle Stages
/ genetics
Models, Molecular
Primary Cell Culture
Protein Binding
Protein Processing, Post-Translational
Protein Structure, Secondary
Protozoan Proteins
/ chemistry
Toxoplasma
/ genetics
Transcription Factors
/ chemistry
Transcription, Genetic
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
22
08
2019
accepted:
23
01
2020
pubmed:
26
2
2020
medline:
17
7
2020
entrez:
26
2
2020
Statut:
ppublish
Résumé
Toxoplasma gondii has a complex life cycle that is typified by asexual development that takes place in vertebrates, and sexual reproduction, which occurs exclusively in felids and is therefore less studied. The developmental transitions rely on changes in the patterns of gene expression, and recent studies have assigned roles for chromatin shapers, including histone modifications, in establishing specific epigenetic programs for each given stage. Here, we identified the T. gondii microrchidia (MORC) protein as an upstream transcriptional repressor of sexual commitment. MORC, in a complex with Apetala 2 (AP2) transcription factors, was shown to recruit the histone deacetylase HDAC3, thereby impeding the accessibility of chromatin at the genes that are exclusively expressed during sexual stages. We found that MORC-depleted cells underwent marked transcriptional changes, resulting in the expression of a specific repertoire of genes, and revealing a shift from asexual proliferation to sexual differentiation. MORC acts as a master regulator that directs the hierarchical expression of secondary AP2 transcription factors, and these transcription factors potentially contribute to the unidirectionality of the life cycle. Thus, MORC plays a cardinal role in the T. gondii life cycle, and its conditional depletion offers a method to study the sexual development of the parasite in vitro, and is proposed as an alternative to the requirement of T. gondii infections in cats.
Identifiants
pubmed: 32094587
doi: 10.1038/s41564-020-0674-4
pii: 10.1038/s41564-020-0674-4
pmc: PMC7104380
mid: EMS85596
doi:
Substances chimiques
Chromatin
0
Histones
0
Protozoan Proteins
0
Transcription Factors
0
Histone Deacetylases
EC 3.5.1.98
histone deacetylase 3
EC 3.5.1.98
Adenosine Triphosphatases
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
570-583Subventions
Organisme : European Research Council
ID : 614880
Pays : International
Commentaires et corrections
Type : CommentIn
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