Promoter-centred chromatin interactions associated with EVI1 expression in EVI1+3q- myeloid leukaemia cells.

EVI1 MECOM chromatin interaction enhancer oncogene regulation

Journal

British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544

Informations de publication

Date de publication:
31 Jan 2024
Historique:
revised: 18 01 2024
received: 06 09 2023
accepted: 19 01 2024
medline: 1 2 2024
pubmed: 1 2 2024
entrez: 31 1 2024
Statut: aheadofprint

Résumé

EVI1 expression is associated with poor prognosis in myeloid leukaemia, which can result from Chr.3q alterations that juxtapose enhancers to induce EVI1 expression via long-range chromatin interactions. More often, however, EVI1 expression occurs unrelated to 3q alterations, and it remained unclear if, in these cases, EVI1 expression is similarly caused by aberrant enhancer activation. Here, we report that, in EVI1+3q- myeloid leukaemia cells, the EVI1 promoter interacts via long-range chromatin interactions with promoters of distally located, active genes, rather than with enhancer elements. Unlike in 3q+ cells, EVI1 expression and long-range interactions appear to not depend on CTCF/cohesin, though EVI1+3q- cells utilise an EVI1 promoter-proximal site to enhance its expression that is also involved in CTCF-mediated looping in 3q+ cells. Long-range interactions in 3q- cells connect EVI1 to promoters of multiple genes, whose transcription correlates with EVI1 in EVI1+3q- cell lines, suggesting a shared mechanism of transcriptional regulation. In line with this, CRISPR interference-induced silencing of two of these sites minimally, but consistently reduced EVI1 expression. Together, we provide novel evidence of features associated with EVI1 expression in 3q- leukaemia and consolidate the view that EVI1 in 3q- leukaemia is largely promoter-driven, potentially involving long-distance promoter clustering.

Identifiants

pubmed: 38296260
doi: 10.1111/bjh.19322
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Imperial Health Charity
ID : FA2021_16
Organisme : Kay Kendall Leukaemia Fund
ID : P71048

Informations de copyright

© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

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Auteurs

Han Leng Ng (HL)

Department of Immunology and Inflammation, Faculty of Medicine, Centre for Haematology, Imperial College London, London, UK.

Mark E Robinson (ME)

Department of Immunology and Inflammation, Faculty of Medicine, Centre for Haematology, Imperial College London, London, UK.
Center of Molecular and Cellular Oncology, Yale University, New Haven, Connecticut, USA.

Philippa C May (PC)

Department of Immunology and Inflammation, Faculty of Medicine, Centre for Haematology, Imperial College London, London, UK.

Andrew J Innes (AJ)

Department of Immunology and Inflammation, Faculty of Medicine, Centre for Haematology, Imperial College London, London, UK.

Christina Hiemeyer (C)

Department of Immunology and Inflammation, Faculty of Medicine, Centre for Haematology, Imperial College London, London, UK.

Niklas Feldhahn (N)

Department of Immunology and Inflammation, Faculty of Medicine, Centre for Haematology, Imperial College London, London, UK.

Classifications MeSH