NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain.

Autor:	Liu S; Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA., Aldinger KA; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA., Cheng CV; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA., Kiyama T; Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA; National Eye Institute, NIH, Bethesda, MD 20892, USA., Dave M; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA., McNamara HK; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA., Zhao W; Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, NY 10016, USA., Stafford JM; Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA., Descostes N; Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA., Lee P; Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA., Caraffi SG; Struttura Semplice Dipartimentale di Genetica Medica, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy., Ivanovski I; Struttura Semplice Dipartimentale di Genetica Medica, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy; Institute of Medical Genetics, University of Zürich, Zürich, Switzerland., Errichiello E; Dipartimento di Medicina Molecolare, Università di Pavia, Pavia, Italy; IRCCS Mondino Foundation, Pavia, Italy., Zweier C; Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 10, 91054 Erlangen, Germany; Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Zuffardi O; Dipartimento di Medicina Molecolare, Università di Pavia, Pavia, Italy., Schneider M; Carle Physicians Group, Section of Neurology, St. Christopher's Hospital for Children, Urbana, IL, USA., Papavasiliou AS; Neurology, IASO Children's Hospital, Athens, Greece., Perry MS; Comprehensive Epilepsy Program, Jane and John Justin Neuroscience Center, Cook Children's Medical Center, Fort Worth, TX 76104, USA., Humberson J; Division of Genetics, Department of Pediatrics, University of Virginia Children's Hospital, Charlottesville, VA, USA., Cho MT; GeneDx, Inc., Gaithersburg, MD, USA., Weber A; Liverpool Women's Hospital, Liverpool, UK., Swale A; Liverpool Women's Hospital, Liverpool, UK; Manchester Centre for Genomic Medicine, Manchester, UK., Badea TC; National Eye Institute, NIH, Bethesda, MD 20892, USA; Research and Development Institute, Transilvania University of Brasov, School of Medicine, Brasov, Romania., Mao CA; Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA; National Eye Institute, NIH, Bethesda, MD 20892, USA., Garavelli L; Struttura Semplice Dipartimentale di Genetica Medica, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy., Dobyns WB; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics (Genetic Medicine), University of Washington, Seattle, WA, USA., Reinberg D; Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: danny.reinberg@nyumc.org.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2021 Nov 18; Vol. 81 (22), pp. 4663-4676.e8. Date of Electronic Publication: 2021 Oct 11.
DOI:	10.1016/j.molcel.2021.09.020
Abstrakt:	The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its HX repeat domain gives rise to misregulation of a subset of developmental genes and curtails motor neuron differentiation of mouse embryonic stem cells. The transcription factor nuclear respiratory factor 1 (NRF1) has a novel and integral role in this neurodevelopmental process, being required for ncPRC1.3 recruitment to chromatin. Competing Interests: Declaration of interests D.R. is a cofounder of Constellation and Fulcrum Pharmaceuticals. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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