Integration of high-throughput reporter assays identify a critical enhancer of the Ikzf1 gene.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2020
Historique:
received: 28 01 2020
accepted: 29 04 2020
entrez: 27 5 2020
pubmed: 27 5 2020
medline: 4 8 2020
Statut: epublish

Résumé

The Ikzf1 locus encodes the lymphoid specific transcription factor Ikaros, which plays an essential role in both T and B cell differentiation, while deregulation or mutation of IKZF1/Ikzf1 is involved in leukemia. Tissue-specific and cell identity genes are usually associated with clusters of enhancers, also called super-enhancers, which are believed to ensure proper regulation of gene expression throughout cell development and differentiation. Several potential regulatory regions have been identified in close proximity of Ikzf1, however, the full extent of the regulatory landscape of the Ikzf1 locus is not yet established. In this study, we combined epigenomics and transcription factor binding along with high-throughput enhancer assay and 4C-seq to prioritize an enhancer element located 120 kb upstream of the Ikzf1 gene. We found that deletion of the E120 enhancer resulted in a significant reduction of Ikzf1 mRNA. However, the epigenetic landscape and 3D topology of the locus were only slightly affected, highlighting the complexity of the regulatory landscape regulating the Ikzf1 locus.

Identifiants

pubmed: 32453736
doi: 10.1371/journal.pone.0233191
pii: PONE-D-20-02571
pmc: PMC7250416
doi:

Substances chimiques

RNA, Messenger 0
Zfpn1a1 protein, mouse 0
Ikaros Transcription Factor 148971-36-2

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0233191

Commentaires et corrections

Type : ErratumIn

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist

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Auteurs

Jaafar Alomairi (J)

Aix-Marseille University, Inserm, TAGC, UMR1090, Marseille, France.
Equipe Labélisée Ligue Contre le Cancer, Marseille, France.

Anne M Molitor (AM)

Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch, France.
CNRS UMR7104, Illkirch, France.
INSERM U1258, Illkirch, France.
University of Strasbourg, Illkirch, France.

Nori Sadouni (N)

Aix-Marseille University, Inserm, TAGC, UMR1090, Marseille, France.
Equipe Labélisée Ligue Contre le Cancer, Marseille, France.

Saadat Hussain (S)

Aix-Marseille University, Inserm, TAGC, UMR1090, Marseille, France.
Equipe Labélisée Ligue Contre le Cancer, Marseille, France.

Magali Torres (M)

Aix-Marseille University, Inserm, TAGC, UMR1090, Marseille, France.
Equipe Labélisée Ligue Contre le Cancer, Marseille, France.

Wiam Saadi (W)

Aix-Marseille University, Inserm, TAGC, UMR1090, Marseille, France.
Equipe Labélisée Ligue Contre le Cancer, Marseille, France.

Lan T M Dao (LTM)

Aix-Marseille University, Inserm, TAGC, UMR1090, Marseille, France.
Equipe Labélisée Ligue Contre le Cancer, Marseille, France.

Guillaume Charbonnier (G)

Aix-Marseille University, Inserm, TAGC, UMR1090, Marseille, France.
Equipe Labélisée Ligue Contre le Cancer, Marseille, France.

David Santiago-Algarra (D)

Aix-Marseille University, Inserm, TAGC, UMR1090, Marseille, France.
Equipe Labélisée Ligue Contre le Cancer, Marseille, France.

Jean Christophe Andrau (JC)

Institut de Génétique Moléculaire de Montpellier, Univ Montpellier, CNRS, Montpellier, France.

Denis Puthier (D)

Aix-Marseille University, Inserm, TAGC, UMR1090, Marseille, France.
Equipe Labélisée Ligue Contre le Cancer, Marseille, France.

Tom Sexton (T)

Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch, France.
CNRS UMR7104, Illkirch, France.
INSERM U1258, Illkirch, France.
University of Strasbourg, Illkirch, France.

Salvatore Spicuglia (S)

Aix-Marseille University, Inserm, TAGC, UMR1090, Marseille, France.
Equipe Labélisée Ligue Contre le Cancer, Marseille, France.

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