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

Pia A Johansson; Per Ludvik Brattås; Christopher H Douse; PingHsun Hsieh; Anita Adami; Julien Pontis; Daniela Grassi; Raquel Garza; Edoardo Sozzi; Rodrigo Cataldo; Marie E Jönsson; Diahann A M Atacho; Karolina Pircs; Feride Eren; Yogita Sharma; Jenny Johansson; Alessandro Fiorenzano; Malin Parmar; Malin Fex; Didier Trono; Evan E Eichler; Johan Jakobsson

doi:10.1016/j.stem.2021.09.008

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

Pia A Johansson, Per Ludvik Brattås, Christopher H Douse, PingHsun Hsieh, Anita Adami, Julien Pontis, Daniela Grassi, Raquel Garza, Edoardo Sozzi, Rodrigo Cataldo, Marie E Jönsson, Diahann A M Atacho, Karolina Pircs, Feride Eren, Yogita Sharma, Jenny Johansson, Alessandro Fiorenzano, Malin Parmar, Malin Fex, Didier TronoEvan E Eichler, Johan Jakobsson

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

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.

Originalspråk	engelska
Sidor (från-till)	52-69.e8
Tidskrift	Cell Stem Cell
Volym	29
Nummer	1
Tidigt onlinedatum	2021
DOI	https://doi.org/10.1016/j.stem.2021.09.008
Status	Published - 2022

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Ämnesklassifikation (UKÄ)

Genetik
Neurovetenskaper
Medicinsk genetik

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10.1016/j.stem.2021.09.008Licens: CC BY

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Johansson, P. A., Brattås, P. L., Douse, C. H., Hsieh, P., Adami, A., Pontis, J., Grassi, D., Garza, R., Sozzi, E., Cataldo, R., Jönsson, M. E., Atacho, D. A. M., Pircs, K., Eren, F., Sharma, Y., Johansson, J., Fiorenzano, A., Parmar, M., Fex, M., ... Jakobsson, J. (2022). A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development. Cell Stem Cell, 29(1), 52-69.e8. https://doi.org/10.1016/j.stem.2021.09.008

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title = "A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development",

abstract = "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.",

author = "Johansson, {Pia A} and Bratt{\aa}s, {Per Ludvik} and Douse, {Christopher H} and PingHsun Hsieh and Anita Adami and Julien Pontis and Daniela Grassi and Raquel Garza and Edoardo Sozzi and Rodrigo Cataldo and J{\"o}nsson, {Marie E} and Atacho, {Diahann A M} and Karolina Pircs and Feride Eren and Yogita Sharma and Jenny Johansson and Alessandro Fiorenzano and Malin Parmar and Malin Fex and Didier Trono and Eichler, {Evan E} and Johan Jakobsson",

year = "2022",

doi = "10.1016/j.stem.2021.09.008",

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Johansson, PA, Brattås, PL, Douse, CH, Hsieh, P, Adami, A, Pontis, J, Grassi, D, Garza, R , Sozzi, E , Cataldo, R , Jönsson, ME , Atacho, DAM , Pircs, K, Eren, F, Sharma, Y, Johansson, J , Fiorenzano, A , Parmar, M , Fex, M, Trono, D, Eichler, EE & Jakobsson, J 2022, 'A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development', Cell Stem Cell, vol. 29, nr. 1, s. 52-69.e8. https://doi.org/10.1016/j.stem.2021.09.008

TY - JOUR

T1 - A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development

AU - Johansson, Pia A

AU - Brattås, Per Ludvik

AU - Douse, Christopher H

AU - Hsieh, PingHsun

AU - Adami, Anita

AU - Pontis, Julien

AU - Grassi, Daniela

AU - Garza, Raquel

AU - Sozzi, Edoardo

AU - Cataldo, Rodrigo

AU - Jönsson, Marie E

AU - Atacho, Diahann A M

AU - Pircs, Karolina

AU - Eren, Feride

AU - Sharma, Yogita

AU - Johansson, Jenny

AU - Fiorenzano, Alessandro

AU - Parmar, Malin

AU - Fex, Malin

AU - Trono, Didier

AU - Eichler, Evan E

AU - Jakobsson, Johan

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1016/j.stem.2021.09.008

DO - 10.1016/j.stem.2021.09.008

M3 - Article

C2 - 34624206

VL - 29

SP - 52-69.e8

JO - Cell Stem Cell

JF - Cell Stem Cell

SN - 1934-5909

IS - 1

ER -

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

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