The scaffolding function of LSD1 controls DNA methylation in mouse ESCs
Malla, Sandhya (Wallenberg Centre for Molecular Medicine. Umeå University)
Kumari, Kanchan (Wallenberg Centre for Molecular Medicine. Umeå University)
García-Prieto, Carlos A. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Caroli, Jonatan (Department of Biology and Biotechnology. University of Pavia)
Nordin, Anna (Department of Biomedical and Clinical Sciences. Division of Molecular Medicine and Virology. Faculty of Medicine and Health Sciences. Linköping University)
Phan, Trinh T.T. (Department of Integrative Biology and Pharmacology. McGovern Medical School. The University of Texas Health Science Center at Houston)
Bhattarai, Devi Prasad (Wallenberg Centre for Molecular Medicine. Umeå University)
Martinez-Gamero, Carlos (Wallenberg Centre for Molecular Medicine. Umeå University)
Dorafshan, Eshagh (Wallenberg Centre for Molecular Medicine. Umeå University)
Stransky, Stephanie (Albert Einstein College of Medicine (Nova York, Estats Units d'Amèrica))
Álvarez-Errico, Damiana (Cancer Epigenetics Group. Josep Carreras Leukaemia Research Institute)
Saiki, Paulina Avovome (Wallenberg Centre for Molecular Medicine. Umeå University)
Lai, Weiyi (State Key Laboratory of Environmental Chemistry and Ecotoxicology. Research Center for Eco-Environmental Sciences. Chinese Academy of Sciences)
Lyu, Cong (State Key Laboratory of Environmental Chemistry and Ecotoxicology. Research Center for Eco-Environmental Sciences. Chinese Academy of Sciences)
Lizana, Ludvig (Department of Physics. Integrated Science Lab. Umeå University)
Gilthorpe, Jonathan D. (Department of Medical and Translational Biology. Umeå University)
Wang, Hailin (State Key Laboratory of Environmental Chemistry and Ecotoxicology. Research Center for Eco-Environmental Sciences. Chinese Academy of Sciences)
Sidoli, Simone (Albert Einstein College of Medicine (Nova York, Estats Units d'Amèrica))
Mateus, Andre (The Laboratory for Molecular Infection Medicine Sweden (MIMS))
Lee, Dung-Fang Lee (Center for Precision Health. McWilliams School of Biomedical Informatics. The University of Texas Health Science Center at Houston)
Cantù, Claudio (Department of Biomedical and Clinical Sciences. Division of Molecular Medicine and Virology. Faculty of Medicine and Health Sciences. Linköping University)
Esteller, M (Universitat de Barcelona. Departament de Ciències Fisiològiques)
Mattevi, Andrea (Department of Biology and Biotechnology. University of Pavia)
Roman, Angel-Carlos (Universidad de Extremadura)
Aguilo, Francesca (Wallenberg Centre for Molecular Medicine. Umeå University)
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	Lysine-specific histone demethylase 1 (LSD1), which demethylates mono- or di- methylated histone H3 on lysine 4 (H3K4me1/2), is essential for early embryogenesis and development. Here we show that LSD1 is dispensable for mouse embryonic stem cell (ESC) self-renewal but is required for mouse ESC growth and differentiation. Reintroduction of a catalytically-impaired LSD1 (LSD1) recovers the proliferation capability of mouse ESCs, yet the enzymatic activity of LSD1 is essential to ensure proper differentiation. Indeed, increased H3K4me1 in Lsd1 knockout (KO) mouse ESCs does not lead to major changes in global gene expression programs related to stemness. However, ablation of LSD1 but not LSD1 results in decreased DNMT1 and UHRF1 proteins coupled to global hypomethylation. We show that both LSD1 and LSD1 control protein stability of UHRF1 and DNMT1 through interaction with HDAC1 and the ubiquitin-specific peptidase 7 (USP7), consequently, facilitating the deacetylation and deubiquitination of DNMT1 and UHRF1. Our studies elucidate a mechanism by which LSD1 controls DNA methylation in mouse ESCs, independently of its lysine demethylase activity.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Animals ; CCAAT-Enhancer-Binding Proteins ; Cell Differentiation ; Cell Proliferation ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA Methylation ; Histone Deacetylase 1 ; Histone Demethylases ; Histones ; Mice ; Mice, Knockout ; Mouse Embryonic Stem Cells ; Ubiquitin-Protein Ligases ; Ubiquitination
Published in:	Nature communications, Vol. 15 Núm. 1 (december 2024) , p. 7758, ISSN 2041-1723

DOI: 10.1038/s41467-024-51966-7
PMID: 39237615

24 p, 5.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles