A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development.

Brain / metabolism DNA-Binding Proteins Gene Expression Regulation Gene Regulatory Networks Humans Organoids / metabolism Transcription Factors / genetics
CRISPRi KRAB-ZNFs brain development chimpanzee evolution forebrain neural progenitors human transposable elements

Journal

Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472

Informations de publication

Date de publication:
06 01 2022
Historique:
received: 20 08 2020
revised: 20 07 2021
accepted: 13 09 2021
pubmed: 9 10 2021
medline: 28 1 2022
entrez: 8 10 2021
Statut: ppublish

Résumé

The human forebrain has expanded in size and complexity compared to chimpanzees despite limited changes in protein-coding genes, suggesting that gene expression regulation is an important driver of brain evolution. Here, we identify a KRAB-ZFP transcription factor, ZNF558, that is expressed in human but not chimpanzee forebrain neural progenitor cells. ZNF558 evolved as a suppressor of LINE-1 transposons but has been co-opted to regulate a single target, the mitophagy gene SPATA18. ZNF558 plays a role in mitochondrial homeostasis, and loss-of-function experiments in cerebral organoids suggests that ZNF558 influences developmental timing during early human brain development. Expression of ZNF558 is controlled by the size of a variable number tandem repeat that is longer in chimpanzees compared to humans, and variable in the human population. Thus, this work provides mechanistic insight into how a cis-acting structural variation establishes a regulatory network that affects human brain evolution.

Identifiants

DOI: 10.1016/j.stem.2021.09.008 PMID: 34624206
pubmed: 34624206
pii: S1934-5909(21)00384-2
doi: 10.1016/j.stem.2021.09.008
pii:
doi:

Substances chimiques

DNA-Binding Proteins 0
Transcription Factors 0
ZNF558 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

52-69.e8

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declarations of interest The authors declare no competing interests.

Auteurs

Pia A Johansson (PA)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.

Per Ludvik Brattås (PL)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.

Christopher H Douse (CH)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.

PingHsun Hsieh (P)

Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

Anita Adami (A)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.

Julien Pontis (J)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Daniela Grassi (D)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.

Raquel Garza (R)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.

Edoardo Sozzi (E)

Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, Lund, Sweden.

Rodrigo Cataldo (R)

Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Lund, Sweden.

Marie E Jönsson (ME)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.

Diahann A M Atacho (DAM)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.

Karolina Pircs (K)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.

Feride Eren (F)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.

Yogita Sharma (Y)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.

Jenny Johansson (J)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.

Alessandro Fiorenzano (A)

Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, Lund, Sweden.

Malin Parmar (M)

Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, Lund, Sweden.

Malin Fex (M)

Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Lund, Sweden.

Didier Trono (D)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Evan E Eichler (EE)

Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.

Johan Jakobsson (J)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden. Electronic address: johan.jakobsson@med.lu.se.

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Classifications MeSH

questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › A cis-acting structural variation at the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de liaison à l'ADN › A cis-acting structural variation at the...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › A cis-acting structural variation at the...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Séquences d'acides nucléiques régulatrices › Réseaux de régulation génique › A cis-acting structural variation at the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A cis-acting structural variation at the...
questionsmedicales.fr › Tissus › Organoïdes › A cis-acting structural variation at the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › A cis-acting structural variation at the...