The epigenetic reader MORC3 is required for T cell development in the thymus
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Summary Cell fate decisions are orchestrated by an interplay of epigenetic factors in collaboration with transcriptional activators and repressors. The epigenetic reader MORC3 is known as a silencer of endogenous retroviruses in mouse embryonic stem cells. Here, we show that mouse MORC3 is expressed in the thymus and reveal that MORC3 loss of function leads to a severe arrest in T cell development at the DN1 stage, accompanied by an expansion of natural killer and myeloid cells. MORC3 function in thymus depends on its ATPase and its ability to bind H3K4me via the CW-type zinc finger domain. We find altered chromatin accessibility at regulatory elements of key T cell transcription factors in DN1 cells and show that re-expressing TCF1 in MORC3-deficient progenitor cells, rescues T cell development. Our work indicates a novel function for MORC3 in modulating regulatory sites essential for T cell lineage commitment at the level of chromatin.
Authors 15
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Veronica Della Chiara Aachen Department of Human Genetics Department of Immunology, Leiden University Medical Centre Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW)
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands
Department of Immunology, Leiden University Medical Centre, Leiden, The Netherlands
Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Leiden University Medical Centre, Leiden, The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Centre, Leiden, The Netherlands
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Gita Naber Aachen Department of Immunology, Leiden University Medical Centre Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW)
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Centre, Leiden, The Netherlands
Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Leiden University Medical Centre, Leiden, The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands
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Christ Leemans Aachen Department of Immunology, Leiden University Medical Centre Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW)
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Centre, Leiden, The Netherlands
Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Leiden University Medical Centre, Leiden, The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands
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University of California, Los Angeles
Affiliation as printed
Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, USA
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Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands
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Kirsten Canté-Barrett Aachen Department of Immunology, Leiden University Medical Centre Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW)
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Centre, Leiden, The Netherlands
Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Leiden University Medical Centre, Leiden, The Netherlands
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Karin Pike‐Overzet Aachen Department of Immunology, Leiden University Medical Centre Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW)
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Centre, Leiden, The Netherlands
Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Leiden University Medical Centre, Leiden, The Netherlands
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Howard Hughes Medical Institute · University of California, Los Angeles
Affiliation as printed
Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, USA
Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA, USA
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Frank J. T. Staal Aachen Department of Immunology, Leiden University Medical Centre Department of Paediatrics, Leiden University Medical Centre Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW)
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Centre, Leiden, The Netherlands
Department of Paediatrics, Leiden University Medical Centre, Leiden, The Netherlands
Novo Nordisk Foundation Centre for Stem Cell Medicine (reNEW), Leiden University Medical Centre, Leiden, The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands
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