Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1
Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 mill...
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| Veröffentlicht in: | Scientific reports 2016-09, Vol.6 (1), p.33887-33887, Article 33887 |
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| creator | Yan, Naihong Cheng, Lin Cho, Kinsang Malik, Muhammad Taimur A. Xiao, Lirong Guo, Chenying Yu, Honghua Zhu, Ruilin Rao, Rajesh C. Chen, Dong Feng |
| description | Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ∼50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT)
Ezh2
from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of
Six1
and its targets. Forced expression of
Six1
in the postnatal retina was sufficient to induce photoreceptor degeneration.
Ezh2
, although enriched in the embryonic retina, was not present in the mature retina; these data reveal an
Ezh2
-mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy. |
| doi_str_mv | 10.1038/srep33887 |
| format | Article |
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Ezh2
from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of
Six1
and its targets. Forced expression of
Six1
in the postnatal retina was sufficient to induce photoreceptor degeneration.
Ezh2
, although enriched in the embryonic retina, was not present in the mature retina; these data reveal an
Ezh2
-mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep33887</identifier><identifier>PMID: 27677711</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>14/63 ; 38/15 ; 38/61 ; 45/29 ; 631/80/304 ; 64/60 ; 692/699/3161/3175 ; Degenerative diseases ; Derepression ; Embryogenesis ; Embryonic growth stage ; Fetuses ; Gene deletion ; Histone methyltransferase ; Homeostasis ; Humanities and Social Sciences ; multidisciplinary ; Photoreceptors ; Retina ; Retinal degeneration ; Science ; Science (multidisciplinary)</subject><ispartof>Scientific reports, 2016-09, Vol.6 (1), p.33887-33887, Article 33887</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Sep 2016</rights><rights>Copyright © 2016, The Author(s) 2016 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-431e7c589bda043d87bd83cce494949cf94ecbe1fcfa7f871e948b9c30c7698c3</citedby><cites>FETCH-LOGICAL-c504t-431e7c589bda043d87bd83cce494949cf94ecbe1fcfa7f871e948b9c30c7698c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039414/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039414/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27915,27916,41111,42180,51567,53782,53784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27677711$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yan, Naihong</creatorcontrib><creatorcontrib>Cheng, Lin</creatorcontrib><creatorcontrib>Cho, Kinsang</creatorcontrib><creatorcontrib>Malik, Muhammad Taimur A.</creatorcontrib><creatorcontrib>Xiao, Lirong</creatorcontrib><creatorcontrib>Guo, Chenying</creatorcontrib><creatorcontrib>Yu, Honghua</creatorcontrib><creatorcontrib>Zhu, Ruilin</creatorcontrib><creatorcontrib>Rao, Rajesh C.</creatorcontrib><creatorcontrib>Chen, Dong Feng</creatorcontrib><title>Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ∼50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT)
Ezh2
from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of
Six1
and its targets. Forced expression of
Six1
in the postnatal retina was sufficient to induce photoreceptor degeneration.
Ezh2
, although enriched in the embryonic retina, was not present in the mature retina; these data reveal an
Ezh2
-mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy.</description><subject>14/63</subject><subject>38/15</subject><subject>38/61</subject><subject>45/29</subject><subject>631/80/304</subject><subject>64/60</subject><subject>692/699/3161/3175</subject><subject>Degenerative diseases</subject><subject>Derepression</subject><subject>Embryogenesis</subject><subject>Embryonic growth stage</subject><subject>Fetuses</subject><subject>Gene deletion</subject><subject>Histone methyltransferase</subject><subject>Homeostasis</subject><subject>Humanities and Social Sciences</subject><subject>multidisciplinary</subject><subject>Photoreceptors</subject><subject>Retina</subject><subject>Retinal degeneration</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkV1LwzAYhYMoKnMX_gEpeKPCNGnSJrkRZMwPEBSc1yFN385Kl8ykFeevN2U6piYXCTkPJy_nIHRI8DnBVFwEDwtKheBbaD_FLBulNE23N-57aBjCK44rSyUjchftpTznnBOyj6aPLrRWt7pJnA3QJq5KPLS1jQ8lzMCC123tbFIsk8aF0OswL_zS2dokk8-XNOILDyH0UBSf6g9ygHYq3QQYfp8D9Hw9mY5vR_cPN3fjq_uRyTBrR4wS4CYTsig1ZrQUvCgFNQaY7LepJANTAKlMpXklOAHJRCENxYbnUhg6QJcr30VXzKE0YFuvG7Xw9Vz7pXK6Vr8VW7-omXtXGaYxCRYNTr4NvHvrILRqXgcDTaMtuC4oImhG80xwEdHjP-ir63yMqaekxNFP5JE6XVHGx7A8VOthCFZ9XWpdV2SPNqdfkz_lROBsBYQo2Rn4jS__uX0B0ICf1A</recordid><startdate>20160928</startdate><enddate>20160928</enddate><creator>Yan, Naihong</creator><creator>Cheng, Lin</creator><creator>Cho, Kinsang</creator><creator>Malik, Muhammad Taimur A.</creator><creator>Xiao, Lirong</creator><creator>Guo, Chenying</creator><creator>Yu, Honghua</creator><creator>Zhu, Ruilin</creator><creator>Rao, Rajesh C.</creator><creator>Chen, Dong Feng</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160928</creationdate><title>Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1</title><author>Yan, Naihong ; 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Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ∼50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT)
Ezh2
from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of
Six1
and its targets. Forced expression of
Six1
in the postnatal retina was sufficient to induce photoreceptor degeneration.
Ezh2
, although enriched in the embryonic retina, was not present in the mature retina; these data reveal an
Ezh2
-mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27677711</pmid><doi>10.1038/srep33887</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 14/63 38/15 38/61 45/29 631/80/304 64/60 692/699/3161/3175 Degenerative diseases Derepression Embryogenesis Embryonic growth stage Fetuses Gene deletion Histone methyltransferase Homeostasis Humanities and Social Sciences multidisciplinary Photoreceptors Retina Retinal degeneration Science Science (multidisciplinary) |
| title | Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1 |
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