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PRC2-mediated repre...
PRC2-mediated repression is essential to maintain identity and function of differentiated dopaminergic and serotonergic neurons
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- Toskas, Konstantinos (author)
- Karolinska Institute,Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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- Yaghmaeian-Salmani, Behzad (author)
- Karolinska Institutet,Karolinska Institute,Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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- Skiteva, Olga (author)
- Karolinska Institutet,Karolinska Institute,Department of Physiology and Pharmacology, Karolinska Institutet, Visionsgatan 4, Solna, Sweden
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- Paslawski, Wojciech (author)
- Karolinska Institutet,Karolinska Institute,Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
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- Gillberg, Linda (author)
- Karolinska Institutet,Karolinska Institute,Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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- Skara, Vasiliki (author)
- Karolinska Institute,Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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- Antoniou, Irene (author)
- Karolinska Institute,Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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- Södersten, Erik (author)
- Karolinska Institute,Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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- Svenningsson, Per (author)
- Karolinska Institutet,Karolinska Institute,Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
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- Chergui, Karima (author)
- Karolinska Institutet,Karolinska Institute,Department of Physiology and Pharmacology, Karolinska Institutet, Visionsgatan 4, Solna, Sweden
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- Ringnér, Markus (author)
- Lund University,Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Molecular Cell Biology,Department of Biology,Faculty of Science,Department of Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Lund University, Sölvegatan 35, Lund, Sweden
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- Perlmann, Thomas (author)
- Karolinska Institutet,Karolinska Institute,Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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- Holmberg, Johan (author)
- Karolinska Institutet,Umeå universitet,Karolinska Institute,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2022
- 2022
- English 20 s.
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:34
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Abstract
Subject headings
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- How neurons can maintain cellular identity over an entire life span remains largely unknown. Here, we show that maintenance of identity in differentiated dopaminergic and serotonergic neurons is critically reliant on the Polycomb repressive complex 2 (PRC2). Deletion of the obligate PRC2 component, Eed, in these neurons resulted in global loss of H3K27me3, followed by a gradual activation of genes harboring both H3K27me3 and H3K9me3 modifications. Notably, H3K9me3 was lost at these PRC2 targets before gene activation. Neuronal survival was not compromised; instead, there was a reduction in subtype-specific gene expression and a progressive impairment of dopaminergic and serotonergic neuronal function, leading to behavioral deficits characteristic of Parkinson's disease and anxiety. Single-cell analysis revealed subtype-specific vulnerability to loss of PRC2 repression in dopamine neurons of the substantia nigra. Our study reveals that a PRC2-dependent nonpermissive chromatin state is essential to maintain the subtype identity and function of dopaminergic and serotonergic neurons.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Toskas, Konstant ...
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Yaghmaeian-Salma ...
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Skiteva, Olga
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Paslawski, Wojci ...
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Gillberg, Linda
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Skara, Vasiliki
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show more...
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Antoniou, Irene
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Södersten, Erik
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Svenningsson, Pe ...
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Chergui, Karima
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Ringnér, Markus
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Perlmann, Thomas
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Holmberg, Johan
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Bioinformatics a ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Science Advances
- By the university
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Lund University
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Umeå University
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Karolinska Institutet