Targeted epigenomic editing ameliorates adult anxiety and excessive drinking after adolescent alcohol exposure
Adolescent binge drinking is a major risk factor for psychiatric disorders later in life including alcohol use disorder. Adolescent alcohol exposure induces epigenetic reprogramming at the enhancer region of the activity-regulated cytoskeleton-associated protein (Arc) immediate-early gene, known as...
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| Veröffentlicht in: | Science advances 2022-05, Vol.8 (18), p.eabn2748 |
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| creator | Bohnsack, John Peyton Zhang, Huaibo Wandling, Gabriela M He, Donghong Kyzar, Evan J Lasek, Amy W Pandey, Subhash C |
| description | Adolescent binge drinking is a major risk factor for psychiatric disorders later in life including alcohol use disorder. Adolescent alcohol exposure induces epigenetic reprogramming at the enhancer region of the activity-regulated cytoskeleton-associated protein (Arc) immediate-early gene, known as synaptic activity response element (SARE), and decreases
expression in the amygdala of both rodents and humans. The causal role of amygdalar epigenomic regulation at
SARE in adult anxiety and drinking after adolescent alcohol exposure is unknown. Here, we show that dCas9-P300 increases histone acetylation at the
SARE and normalizes deficits in
expression, leading to attenuation of adult anxiety and excessive alcohol drinking in a rat model of adolescent alcohol exposure. Conversely, dCas9-KRAB increases repressive histone methylation at the
SARE, decreases
expression, and produces anxiety and alcohol drinking in control rats. These results demonstrate that epigenomic editing in the amygdala can ameliorate adult psychopathology after adolescent alcohol exposure. |
| doi_str_mv | 10.1126/sciadv.abn2748 |
| format | Article |
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expression in the amygdala of both rodents and humans. The causal role of amygdalar epigenomic regulation at
SARE in adult anxiety and drinking after adolescent alcohol exposure is unknown. Here, we show that dCas9-P300 increases histone acetylation at the
SARE and normalizes deficits in
expression, leading to attenuation of adult anxiety and excessive alcohol drinking in a rat model of adolescent alcohol exposure. Conversely, dCas9-KRAB increases repressive histone methylation at the
SARE, decreases
expression, and produces anxiety and alcohol drinking in control rats. These results demonstrate that epigenomic editing in the amygdala can ameliorate adult psychopathology after adolescent alcohol exposure.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.abn2748</identifier><identifier>PMID: 35507645</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Adolescent ; Alcoholism - genetics ; Animals ; Anxiety - genetics ; Diseases and Disorders ; Epigenomics ; Ethanol - adverse effects ; Histones - metabolism ; Humans ; Neuroscience ; Rats ; SciAdv r-articles</subject><ispartof>Science advances, 2022-05, Vol.8 (18), p.eabn2748</ispartof><rights>Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2022 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-39d7f0bb285011ea7794737b6780767de895dc7ec8c088a5509c8b98ca0729923</citedby><cites>FETCH-LOGICAL-c456t-39d7f0bb285011ea7794737b6780767de895dc7ec8c088a5509c8b98ca0729923</cites><orcidid>0000-0001-7139-8464 ; 0000-0002-7688-0281 ; 0000-0002-7099-2442 ; 0000-0002-0961-4426 ; 0000-0002-8713-4436</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067919/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067919/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35507645$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bohnsack, John Peyton</creatorcontrib><creatorcontrib>Zhang, Huaibo</creatorcontrib><creatorcontrib>Wandling, Gabriela M</creatorcontrib><creatorcontrib>He, Donghong</creatorcontrib><creatorcontrib>Kyzar, Evan J</creatorcontrib><creatorcontrib>Lasek, Amy W</creatorcontrib><creatorcontrib>Pandey, Subhash C</creatorcontrib><title>Targeted epigenomic editing ameliorates adult anxiety and excessive drinking after adolescent alcohol exposure</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>Adolescent binge drinking is a major risk factor for psychiatric disorders later in life including alcohol use disorder. Adolescent alcohol exposure induces epigenetic reprogramming at the enhancer region of the activity-regulated cytoskeleton-associated protein (Arc) immediate-early gene, known as synaptic activity response element (SARE), and decreases
expression in the amygdala of both rodents and humans. The causal role of amygdalar epigenomic regulation at
SARE in adult anxiety and drinking after adolescent alcohol exposure is unknown. Here, we show that dCas9-P300 increases histone acetylation at the
SARE and normalizes deficits in
expression, leading to attenuation of adult anxiety and excessive alcohol drinking in a rat model of adolescent alcohol exposure. Conversely, dCas9-KRAB increases repressive histone methylation at the
SARE, decreases
expression, and produces anxiety and alcohol drinking in control rats. These results demonstrate that epigenomic editing in the amygdala can ameliorate adult psychopathology after adolescent alcohol exposure.</description><subject>Adolescent</subject><subject>Alcoholism - genetics</subject><subject>Animals</subject><subject>Anxiety - genetics</subject><subject>Diseases and Disorders</subject><subject>Epigenomics</subject><subject>Ethanol - adverse effects</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Neuroscience</subject><subject>Rats</subject><subject>SciAdv r-articles</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUMtOwzAQtBCIVqVXjig_0GIncWxfkFDFS6rEpZwtx96khiSO7LRq_x6XlgpOs9LOzM4OQrcEzwlJi_ugrTLbuSq7lOX8Ao3TjNFZSnN--WceoWkInxhjkhcFJeIajTJKMStyOkbdSvkaBjAJ9LaGzrVWJ2DsYLs6US001nk1QEiU2TRDorqdhWEfMQp2GkKwW0iMt93Xj6AawEeqayBo6CK_0W7tmsjtXdh4uEFXlWoCTE84QR_PT6vF62z5_vK2eFzOdE6LYZYJwypclimnmBBQjImcZawsGI-5mQEuqNEMNNeYcxW_EZqXgmuFWSpEmk3Qw9G335QtmEMWrxrZe9sqv5dOWfl_09m1rN1WClwwQUQ0mB8NtHcheKjOWoLloXx5LF-eyo-Cu78Xz_TfqrNvzG6F9w</recordid><startdate>20220506</startdate><enddate>20220506</enddate><creator>Bohnsack, John Peyton</creator><creator>Zhang, Huaibo</creator><creator>Wandling, Gabriela M</creator><creator>He, Donghong</creator><creator>Kyzar, Evan J</creator><creator>Lasek, Amy W</creator><creator>Pandey, Subhash C</creator><general>American Association for the Advancement of Science</general><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>5PM</scope><orcidid>https://orcid.org/0000-0001-7139-8464</orcidid><orcidid>https://orcid.org/0000-0002-7688-0281</orcidid><orcidid>https://orcid.org/0000-0002-7099-2442</orcidid><orcidid>https://orcid.org/0000-0002-0961-4426</orcidid><orcidid>https://orcid.org/0000-0002-8713-4436</orcidid></search><sort><creationdate>20220506</creationdate><title>Targeted epigenomic editing ameliorates adult anxiety and excessive drinking after adolescent alcohol exposure</title><author>Bohnsack, John Peyton ; Zhang, Huaibo ; Wandling, Gabriela M ; He, Donghong ; Kyzar, Evan J ; Lasek, Amy W ; Pandey, Subhash C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-39d7f0bb285011ea7794737b6780767de895dc7ec8c088a5509c8b98ca0729923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adolescent</topic><topic>Alcoholism - genetics</topic><topic>Animals</topic><topic>Anxiety - genetics</topic><topic>Diseases and Disorders</topic><topic>Epigenomics</topic><topic>Ethanol - adverse effects</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Neuroscience</topic><topic>Rats</topic><topic>SciAdv r-articles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bohnsack, John Peyton</creatorcontrib><creatorcontrib>Zhang, Huaibo</creatorcontrib><creatorcontrib>Wandling, Gabriela M</creatorcontrib><creatorcontrib>He, Donghong</creatorcontrib><creatorcontrib>Kyzar, Evan J</creatorcontrib><creatorcontrib>Lasek, Amy W</creatorcontrib><creatorcontrib>Pandey, Subhash C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bohnsack, John Peyton</au><au>Zhang, Huaibo</au><au>Wandling, Gabriela M</au><au>He, Donghong</au><au>Kyzar, Evan J</au><au>Lasek, Amy W</au><au>Pandey, Subhash C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeted epigenomic editing ameliorates adult anxiety and excessive drinking after adolescent alcohol exposure</atitle><jtitle>Science advances</jtitle><addtitle>Sci Adv</addtitle><date>2022-05-06</date><risdate>2022</risdate><volume>8</volume><issue>18</issue><spage>eabn2748</spage><pages>eabn2748-</pages><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>Adolescent binge drinking is a major risk factor for psychiatric disorders later in life including alcohol use disorder. Adolescent alcohol exposure induces epigenetic reprogramming at the enhancer region of the activity-regulated cytoskeleton-associated protein (Arc) immediate-early gene, known as synaptic activity response element (SARE), and decreases
expression in the amygdala of both rodents and humans. The causal role of amygdalar epigenomic regulation at
SARE in adult anxiety and drinking after adolescent alcohol exposure is unknown. Here, we show that dCas9-P300 increases histone acetylation at the
SARE and normalizes deficits in
expression, leading to attenuation of adult anxiety and excessive alcohol drinking in a rat model of adolescent alcohol exposure. Conversely, dCas9-KRAB increases repressive histone methylation at the
SARE, decreases
expression, and produces anxiety and alcohol drinking in control rats. These results demonstrate that epigenomic editing in the amygdala can ameliorate adult psychopathology after adolescent alcohol exposure.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>35507645</pmid><doi>10.1126/sciadv.abn2748</doi><orcidid>https://orcid.org/0000-0001-7139-8464</orcidid><orcidid>https://orcid.org/0000-0002-7688-0281</orcidid><orcidid>https://orcid.org/0000-0002-7099-2442</orcidid><orcidid>https://orcid.org/0000-0002-0961-4426</orcidid><orcidid>https://orcid.org/0000-0002-8713-4436</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Alcoholism - genetics Animals Anxiety - genetics Diseases and Disorders Epigenomics Ethanol - adverse effects Histones - metabolism Humans Neuroscience Rats SciAdv r-articles |
| title | Targeted epigenomic editing ameliorates adult anxiety and excessive drinking after adolescent alcohol exposure |
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