Identification of long regulatory elements in the genome of Plasmodium falciparum and other eukaryotes.


Journal

PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922

Informations de publication

Date de publication:
04 2021
Historique:
received: 07 09 2020
accepted: 24 03 2021
revised: 28 04 2021
pubmed: 17 4 2021
medline: 15 9 2021
entrez: 16 4 2021
Statut: epublish

Résumé

Long regulatory elements (LREs), such as CpG islands, polydA:dT tracts or AU-rich elements, are thought to play key roles in gene regulation but, as opposed to conventional binding sites of transcription factors, few methods have been proposed to formally and automatically characterize them. We present here a computational approach named DExTER (Domain Exploration To Explain gene Regulation) dedicated to the identification of candidate LREs (cLREs) and apply it to the analysis of the genomes of P. falciparum and other eukaryotes. Our analyses show that all tested genomes contain several cLREs that are somewhat conserved along evolution, and that gene expression can be predicted with surprising accuracy on the basis of these long regions only. Regulation by cLREs exhibits very different behaviours depending on species and conditions. In P. falciparum and other Apicomplexan organisms as well as in Dictyostelium discoideum, the process appears highly dynamic, with different cLREs involved at different phases of the life cycle. For multicellular organisms, the same cLREs are involved in all tissues, but a dynamic behavior is observed along embryonic development stages. In P. falciparum, whose genome is known to be strongly depleted of transcription factors, cLREs are predictive of expression with an accuracy above 70%, and our analyses show that they are associated with both transcriptional and post-transcriptional regulation signals. Moreover, we assessed the biological relevance of one LRE discovered by DExTER in P. falciparum using an in vivo reporter assay. The source code (python) of DExTER is available at https://gite.lirmm.fr/menichelli/DExTER.

Identifiants

pubmed: 33861755
doi: 10.1371/journal.pcbi.1008909
pii: PCOMPBIOL-D-20-01622
pmc: PMC8081344
doi:

Substances chimiques

Histones 0
RNA, Antisense 0
RNA, Messenger 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1008909

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Christophe Menichelli (C)

LIRMM, Univ Montpellier, CNRS, Montpellier, France.

Vincent Guitard (V)

Laboratory of Pathogen-Host Interactions (LPHI), UMR5235, CNRS, Montpellier University, INSERM, Montpellier, France.

Rafael M Martins (RM)

Laboratory of Pathogen-Host Interactions (LPHI), UMR5235, CNRS, Montpellier University, INSERM, Montpellier, France.

Sophie Lèbre (S)

IMAG, Univ. Montpellier, CNRS, Montpellier, France.
Univ. Paul-Valéry-Montpellier 3, Montpellier, France.

Jose-Juan Lopez-Rubio (JJ)

Laboratory of Pathogen-Host Interactions (LPHI), UMR5235, CNRS, Montpellier University, INSERM, Montpellier, France.

Charles-Henri Lecellier (CH)

LIRMM, Univ Montpellier, CNRS, Montpellier, France.
Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France.

Laurent Bréhélin (L)

LIRMM, Univ Montpellier, CNRS, Montpellier, France.

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Classifications MeSH