A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development
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...
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| Veröffentlicht in: | Cell stem cell 2022-01, Vol.29 (1), p.52-69.e8 |
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| creator | Johansson, Pia A. Brattås, Per Ludvik Douse, Christopher H. Hsieh, PingHsun Adami, Anita Pontis, Julien Grassi, Daniela Garza, Raquel Sozzi, Edoardo Cataldo, Rodrigo Jönsson, Marie E. Atacho, Diahann A.M. Pircs, Karolina Eren, Feride Sharma, Yogita Johansson, Jenny Fiorenzano, Alessandro Parmar, Malin Fex, Malin Trono, Didier Eichler, Evan E. Jakobsson, Johan |
| description | 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.
[Display omitted]
•ZNF558 is uniquely expressed in human but not chimpanzee forebrain progenitors•ZNF558 has been co-opted to control the expression of a single gene, SPATA18•ZNF558 plays a role in mitochondrial homeostasis and brain development•ZNF558 expression is controlled by the size of a downstream VNTR
Johansson et al. identify ZNF558, a KRAB-ZFP expressed in human but not chimpanzee forebrain progenitors, where it regulates its target SPATA18. The expression of ZNF558 is controlled by the size of a VNTR that is longer in chimpanzees compared to humans, demonstrating a role for structural variations in human brain evolution. |
| doi_str_mv | 10.1016/j.stem.2021.09.008 |
| format | Article |
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[Display omitted]
•ZNF558 is uniquely expressed in human but not chimpanzee forebrain progenitors•ZNF558 has been co-opted to control the expression of a single gene, SPATA18•ZNF558 plays a role in mitochondrial homeostasis and brain development•ZNF558 expression is controlled by the size of a downstream VNTR
Johansson et al. identify ZNF558, a KRAB-ZFP expressed in human but not chimpanzee forebrain progenitors, where it regulates its target SPATA18. The expression of ZNF558 is controlled by the size of a VNTR that is longer in chimpanzees compared to humans, demonstrating a role for structural variations in human brain evolution.</description><identifier>ISSN: 1934-5909</identifier><identifier>EISSN: 1875-9777</identifier><identifier>DOI: 10.1016/j.stem.2021.09.008</identifier><identifier>PMID: 34624206</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Basic Medicine ; Biologi ; Biological Sciences ; Brain - metabolism ; brain development ; chimpanzee ; CRISPRi ; DNA-Binding Proteins ; evolution ; forebrain neural progenitors ; Gene Expression Regulation ; Gene Regulatory Networks ; Genetics ; Genetik ; human ; Humans ; KRAB-ZNFs ; Medical and Health Sciences ; Medical Genetics ; Medicin och hälsovetenskap ; Medicinsk genetik ; Medicinska och farmaceutiska grundvetenskaper ; Natural Sciences ; Naturvetenskap ; Neurosciences ; Neurovetenskaper ; Organoids - metabolism ; Transcription Factors - genetics ; Transcription Factors - metabolism ; transposable elements</subject><ispartof>Cell stem cell, 2022-01, Vol.29 (1), p.52-69.e8</ispartof><rights>2021 Elsevier Inc.</rights><rights>Copyright © 2021 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c507t-f1cb2e36f6c9d2e1d4f9ae5f03237b587954dd876fc3075606ae7b229416bcfe3</citedby><cites>FETCH-LOGICAL-c507t-f1cb2e36f6c9d2e1d4f9ae5f03237b587954dd876fc3075606ae7b229416bcfe3</cites><orcidid>0000-0002-6158-0235 ; 0000-0003-1225-414X ; 0000-0002-2524-3055 ; 0000-0001-8281-4785 ; 0000-0002-0110-2522</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1934590921003842$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,550,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34624206$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://lup.lub.lu.se/record/b78aae61-c5c5-4cb5-8d81-21ac22d249f1$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:149831343$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Johansson, Pia A.</creatorcontrib><creatorcontrib>Brattås, Per Ludvik</creatorcontrib><creatorcontrib>Douse, Christopher H.</creatorcontrib><creatorcontrib>Hsieh, PingHsun</creatorcontrib><creatorcontrib>Adami, Anita</creatorcontrib><creatorcontrib>Pontis, Julien</creatorcontrib><creatorcontrib>Grassi, Daniela</creatorcontrib><creatorcontrib>Garza, Raquel</creatorcontrib><creatorcontrib>Sozzi, Edoardo</creatorcontrib><creatorcontrib>Cataldo, Rodrigo</creatorcontrib><creatorcontrib>Jönsson, Marie E.</creatorcontrib><creatorcontrib>Atacho, Diahann A.M.</creatorcontrib><creatorcontrib>Pircs, Karolina</creatorcontrib><creatorcontrib>Eren, Feride</creatorcontrib><creatorcontrib>Sharma, Yogita</creatorcontrib><creatorcontrib>Johansson, Jenny</creatorcontrib><creatorcontrib>Fiorenzano, Alessandro</creatorcontrib><creatorcontrib>Parmar, Malin</creatorcontrib><creatorcontrib>Fex, Malin</creatorcontrib><creatorcontrib>Trono, Didier</creatorcontrib><creatorcontrib>Eichler, Evan E.</creatorcontrib><creatorcontrib>Jakobsson, Johan</creatorcontrib><title>A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development</title><title>Cell stem cell</title><addtitle>Cell Stem Cell</addtitle><description>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.
[Display omitted]
•ZNF558 is uniquely expressed in human but not chimpanzee forebrain progenitors•ZNF558 has been co-opted to control the expression of a single gene, SPATA18•ZNF558 plays a role in mitochondrial homeostasis and brain development•ZNF558 expression is controlled by the size of a downstream VNTR
Johansson et al. identify ZNF558, a KRAB-ZFP expressed in human but not chimpanzee forebrain progenitors, where it regulates its target SPATA18. The expression of ZNF558 is controlled by the size of a VNTR that is longer in chimpanzees compared to humans, demonstrating a role for structural variations in human brain evolution.</description><subject>Basic Medicine</subject><subject>Biologi</subject><subject>Biological Sciences</subject><subject>Brain - metabolism</subject><subject>brain development</subject><subject>chimpanzee</subject><subject>CRISPRi</subject><subject>DNA-Binding Proteins</subject><subject>evolution</subject><subject>forebrain neural progenitors</subject><subject>Gene Expression Regulation</subject><subject>Gene Regulatory Networks</subject><subject>Genetics</subject><subject>Genetik</subject><subject>human</subject><subject>Humans</subject><subject>KRAB-ZNFs</subject><subject>Medical and Health Sciences</subject><subject>Medical Genetics</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicinsk genetik</subject><subject>Medicinska och farmaceutiska grundvetenskaper</subject><subject>Natural Sciences</subject><subject>Naturvetenskap</subject><subject>Neurosciences</subject><subject>Neurovetenskaper</subject><subject>Organoids - metabolism</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>transposable elements</subject><issn>1934-5909</issn><issn>1875-9777</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp9kUtv1DAUhSMEoqXwB1ggL9kk2I6fEpuqooA0gg1s2FiOczP1NIkHP6bqv8ejGbqDxdU9uvrOseTTNG8J7ggm4sOuSxmWjmJKOqw7jNWz5pIoyVstpXxete5ZyzXWF82rlHYYc0mwfNlc9ExQRrG4bNI1cj611mW_blHKsbhcop3RwUZvsw8rshnlO0C_vt1yrtAcXEnIhTXHMCdk0RZWQBG2ZbY5xEe0Qn4I8R75Fd2Vxa5oiLbqEQ4wh_0Ca37dvJjsnODNeV81P28__bj50m6-f_56c71pHccytxNxA4VeTMLpkQIZ2aQt8An3tJcDV1JzNo5Kisn1WHKBhQU5UKoZEYOboL9q2lNueoB9Gcw--sXGRxOsN-fTfVVgGFeM88pv_snPZV9nqHM0DFJZC4IYxx03zA3cqFERQ4l1lI6U6YnUuPenuH0MvwukbBafHMyzXSGUZChXWGhNGK4oPaEuhpQiTE9vE2yOXZudOXZtjl0brE3tuprenfPLsMD4ZPlbbgU-ngCon3zwEE1yHlYHo4_gshmD_1_-HwKpvKs</recordid><startdate>20220106</startdate><enddate>20220106</enddate><creator>Johansson, Pia A.</creator><creator>Brattås, Per Ludvik</creator><creator>Douse, Christopher H.</creator><creator>Hsieh, PingHsun</creator><creator>Adami, Anita</creator><creator>Pontis, Julien</creator><creator>Grassi, Daniela</creator><creator>Garza, Raquel</creator><creator>Sozzi, Edoardo</creator><creator>Cataldo, Rodrigo</creator><creator>Jönsson, Marie E.</creator><creator>Atacho, Diahann A.M.</creator><creator>Pircs, Karolina</creator><creator>Eren, Feride</creator><creator>Sharma, Yogita</creator><creator>Johansson, Jenny</creator><creator>Fiorenzano, Alessandro</creator><creator>Parmar, Malin</creator><creator>Fex, Malin</creator><creator>Trono, Didier</creator><creator>Eichler, Evan E.</creator><creator>Jakobsson, Johan</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AGCHP</scope><scope>AOWAS</scope><scope>D8T</scope><scope>D95</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0002-6158-0235</orcidid><orcidid>https://orcid.org/0000-0003-1225-414X</orcidid><orcidid>https://orcid.org/0000-0002-2524-3055</orcidid><orcidid>https://orcid.org/0000-0001-8281-4785</orcidid><orcidid>https://orcid.org/0000-0002-0110-2522</orcidid></search><sort><creationdate>20220106</creationdate><title>A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development</title><author>Johansson, Pia A. ; 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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.
[Display omitted]
•ZNF558 is uniquely expressed in human but not chimpanzee forebrain progenitors•ZNF558 has been co-opted to control the expression of a single gene, SPATA18•ZNF558 plays a role in mitochondrial homeostasis and brain development•ZNF558 expression is controlled by the size of a downstream VNTR
Johansson et al. identify ZNF558, a KRAB-ZFP expressed in human but not chimpanzee forebrain progenitors, where it regulates its target SPATA18. The expression of ZNF558 is controlled by the size of a VNTR that is longer in chimpanzees compared to humans, demonstrating a role for structural variations in human brain evolution.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>34624206</pmid><doi>10.1016/j.stem.2021.09.008</doi><orcidid>https://orcid.org/0000-0002-6158-0235</orcidid><orcidid>https://orcid.org/0000-0003-1225-414X</orcidid><orcidid>https://orcid.org/0000-0002-2524-3055</orcidid><orcidid>https://orcid.org/0000-0001-8281-4785</orcidid><orcidid>https://orcid.org/0000-0002-0110-2522</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online |
| subjects | Basic Medicine Biologi Biological Sciences Brain - metabolism brain development chimpanzee CRISPRi DNA-Binding Proteins evolution forebrain neural progenitors Gene Expression Regulation Gene Regulatory Networks Genetics Genetik human Humans KRAB-ZNFs Medical and Health Sciences Medical Genetics Medicin och hälsovetenskap Medicinsk genetik Medicinska och farmaceutiska grundvetenskaper Natural Sciences Naturvetenskap Neurosciences Neurovetenskaper Organoids - metabolism Transcription Factors - genetics Transcription Factors - metabolism transposable elements |
| title | A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development |
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