Geometric regulation of histone state directs melanoma reprogramming
Malignant melanoma displays a high degree of cellular plasticity during disease progression. Signals in the tumor microenvironment are believed to influence melanoma plasticity through changes in the epigenetic state to guide dynamic differentiation and de-differentiation. Here we uncover a relation...
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Veröffentlicht in: | Communications biology 2020-07, Vol.3 (1), p.341-341, Article 341 |
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description | Malignant melanoma displays a high degree of cellular plasticity during disease progression. Signals in the tumor microenvironment are believed to influence melanoma plasticity through changes in the epigenetic state to guide dynamic differentiation and de-differentiation. Here we uncover a relationship between geometric features at perimeter regions of melanoma aggregates, and reprogramming to a stem cell-like state through histone marks H3K4Me2 and H3K9Ac. Using an in vitro tumor microengineering approach, we find spatial enrichment of these histone modifications with concurrent expression of stemness markers. The epigenetic modifier
PRDM14
overlaps with H3K9Ac and shows elevated expression in cells along regions of perimeter curvature. siRNA knockdown of
PRDM14
abolishes the MIC phenotype suggesting a role in regulating melanoma heterogeneity. Our results suggest mechanotransduction at the periphery of melanoma aggregates may orchestrate the activity of epigenetic modifiers to regulate histone state, cellular plasticity, and tumorigenicity.
Junmin Lee et al. study the role of geometric features at the perimeter regions of melanoma aggregates in programming stem cell-like state through histone marks. They use a tumor microengineering approach in vitro and report a spatial enrichment of histone modifications with stemness markers. Their work uncovers a mechanotransduction signaling that regulates epigenetic modifiers to regulate tumorigenicity. |
doi_str_mv | 10.1038/s42003-020-1067-1 |
format | Article |
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PRDM14
overlaps with H3K9Ac and shows elevated expression in cells along regions of perimeter curvature. siRNA knockdown of
PRDM14
abolishes the MIC phenotype suggesting a role in regulating melanoma heterogeneity. Our results suggest mechanotransduction at the periphery of melanoma aggregates may orchestrate the activity of epigenetic modifiers to regulate histone state, cellular plasticity, and tumorigenicity.
Junmin Lee et al. study the role of geometric features at the perimeter regions of melanoma aggregates in programming stem cell-like state through histone marks. They use a tumor microengineering approach in vitro and report a spatial enrichment of histone modifications with stemness markers. Their work uncovers a mechanotransduction signaling that regulates epigenetic modifiers to regulate tumorigenicity.</description><identifier>ISSN: 2399-3642</identifier><identifier>EISSN: 2399-3642</identifier><identifier>DOI: 10.1038/s42003-020-1067-1</identifier><identifier>PMID: 32620903</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/100 ; 13/106 ; 13/107 ; 45/15 ; 631/532 ; 631/57 ; 631/67 ; 692/699 ; Biology ; Biomedical and Life Sciences ; Epigenetics ; Life Sciences ; Mechanotransduction ; Melanoma ; Phenotypes ; Plasticity ; siRNA ; Skin cancer ; Stem cells ; Tumorigenicity</subject><ispartof>Communications biology, 2020-07, Vol.3 (1), p.341-341, Article 341</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-153bc8304d23fd62c51b1fe200a5acf489c2033a60a4bdecc2b4ccd2dd2e24133</citedby><cites>FETCH-LOGICAL-c536t-153bc8304d23fd62c51b1fe200a5acf489c2033a60a4bdecc2b4ccd2dd2e24133</cites><orcidid>0000-0001-8583-5397 ; 0000-0003-1046-7387 ; 0000-0002-8963-9796 ; 0000-0003-4071-6620 ; 0000-0002-4414-7130 ; 0000-0002-0536-0190 ; 0000-0001-9919-2441</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/PMC7334222/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334222/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32620903$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Junmin</creatorcontrib><creatorcontrib>Molley, Thomas G.</creatorcontrib><creatorcontrib>Seward, Christopher H.</creatorcontrib><creatorcontrib>Abdeen, Amr A.</creatorcontrib><creatorcontrib>Zhang, Huimin</creatorcontrib><creatorcontrib>Wang, Xiaochun</creatorcontrib><creatorcontrib>Gandhi, Hetvi</creatorcontrib><creatorcontrib>Yang, Jia-Lin</creatorcontrib><creatorcontrib>Gaus, Katharina</creatorcontrib><creatorcontrib>Kilian, Kristopher A.</creatorcontrib><title>Geometric regulation of histone state directs melanoma reprogramming</title><title>Communications biology</title><addtitle>Commun Biol</addtitle><addtitle>Commun Biol</addtitle><description>Malignant melanoma displays a high degree of cellular plasticity during disease progression. Signals in the tumor microenvironment are believed to influence melanoma plasticity through changes in the epigenetic state to guide dynamic differentiation and de-differentiation. Here we uncover a relationship between geometric features at perimeter regions of melanoma aggregates, and reprogramming to a stem cell-like state through histone marks H3K4Me2 and H3K9Ac. Using an in vitro tumor microengineering approach, we find spatial enrichment of these histone modifications with concurrent expression of stemness markers. The epigenetic modifier
PRDM14
overlaps with H3K9Ac and shows elevated expression in cells along regions of perimeter curvature. siRNA knockdown of
PRDM14
abolishes the MIC phenotype suggesting a role in regulating melanoma heterogeneity. Our results suggest mechanotransduction at the periphery of melanoma aggregates may orchestrate the activity of epigenetic modifiers to regulate histone state, cellular plasticity, and tumorigenicity.
Junmin Lee et al. study the role of geometric features at the perimeter regions of melanoma aggregates in programming stem cell-like state through histone marks. They use a tumor microengineering approach in vitro and report a spatial enrichment of histone modifications with stemness markers. Their work uncovers a mechanotransduction signaling that regulates epigenetic modifiers to regulate tumorigenicity.</description><subject>13/100</subject><subject>13/106</subject><subject>13/107</subject><subject>45/15</subject><subject>631/532</subject><subject>631/57</subject><subject>631/67</subject><subject>692/699</subject><subject>Biology</subject><subject>Biomedical and Life Sciences</subject><subject>Epigenetics</subject><subject>Life Sciences</subject><subject>Mechanotransduction</subject><subject>Melanoma</subject><subject>Phenotypes</subject><subject>Plasticity</subject><subject>siRNA</subject><subject>Skin cancer</subject><subject>Stem cells</subject><subject>Tumorigenicity</subject><issn>2399-3642</issn><issn>2399-3642</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kUFr3DAQhUVpSUKaH5BLMeTSi1tpRpZXl0BI2qQQ6KU9C1keOwq2tZXkQv59tGyaJoWeZmC-eaOnx9ip4J8Ex83nJIFzrDnwWnDV1uINOwLUukYl4e2L_pCdpHTPORdaa4XygB0iKOCa4xG7uqYwU47eVZHGdbLZh6UKQ3XnUw4LVSnbTFXvI7mcqpkmu4TZFngbwxjtPPtlfM_eDXZKdPJUj9nPr19-XN7Ut9-vv11e3NauQZVr0WDnNshlDzj0ClwjOjFQsWEb6wa50Q44olXcyq4n56CTzvXQ90AgBeIxO9_rbtdupt7RkqOdzDb62cYHE6w3ryeLvzNj-G1aRAkAReDjk0AMv1ZK2cw-OZqKKQprMlD-VDRNq3a3zv5B78Mal2KvUEK3rVZ8R4k95WJIKdLw_BjBzS4ms4_JlJjMLiYjys6Hly6eN_6EUgDYA6mMlpHi39P_V30ECx6eMQ</recordid><startdate>20200703</startdate><enddate>20200703</enddate><creator>Lee, Junmin</creator><creator>Molley, Thomas G.</creator><creator>Seward, Christopher H.</creator><creator>Abdeen, Amr A.</creator><creator>Zhang, Huimin</creator><creator>Wang, Xiaochun</creator><creator>Gandhi, Hetvi</creator><creator>Yang, Jia-Lin</creator><creator>Gaus, Katharina</creator><creator>Kilian, Kristopher A.</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>7XB</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2P</scope><scope>M7P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PKEHL</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8583-5397</orcidid><orcidid>https://orcid.org/0000-0003-1046-7387</orcidid><orcidid>https://orcid.org/0000-0002-8963-9796</orcidid><orcidid>https://orcid.org/0000-0003-4071-6620</orcidid><orcidid>https://orcid.org/0000-0002-4414-7130</orcidid><orcidid>https://orcid.org/0000-0002-0536-0190</orcidid><orcidid>https://orcid.org/0000-0001-9919-2441</orcidid></search><sort><creationdate>20200703</creationdate><title>Geometric regulation of histone state directs melanoma reprogramming</title><author>Lee, Junmin ; 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Signals in the tumor microenvironment are believed to influence melanoma plasticity through changes in the epigenetic state to guide dynamic differentiation and de-differentiation. Here we uncover a relationship between geometric features at perimeter regions of melanoma aggregates, and reprogramming to a stem cell-like state through histone marks H3K4Me2 and H3K9Ac. Using an in vitro tumor microengineering approach, we find spatial enrichment of these histone modifications with concurrent expression of stemness markers. The epigenetic modifier
PRDM14
overlaps with H3K9Ac and shows elevated expression in cells along regions of perimeter curvature. siRNA knockdown of
PRDM14
abolishes the MIC phenotype suggesting a role in regulating melanoma heterogeneity. Our results suggest mechanotransduction at the periphery of melanoma aggregates may orchestrate the activity of epigenetic modifiers to regulate histone state, cellular plasticity, and tumorigenicity.
Junmin Lee et al. study the role of geometric features at the perimeter regions of melanoma aggregates in programming stem cell-like state through histone marks. They use a tumor microengineering approach in vitro and report a spatial enrichment of histone modifications with stemness markers. Their work uncovers a mechanotransduction signaling that regulates epigenetic modifiers to regulate tumorigenicity.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32620903</pmid><doi>10.1038/s42003-020-1067-1</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-8583-5397</orcidid><orcidid>https://orcid.org/0000-0003-1046-7387</orcidid><orcidid>https://orcid.org/0000-0002-8963-9796</orcidid><orcidid>https://orcid.org/0000-0003-4071-6620</orcidid><orcidid>https://orcid.org/0000-0002-4414-7130</orcidid><orcidid>https://orcid.org/0000-0002-0536-0190</orcidid><orcidid>https://orcid.org/0000-0001-9919-2441</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 13/100 13/106 13/107 45/15 631/532 631/57 631/67 692/699 Biology Biomedical and Life Sciences Epigenetics Life Sciences Mechanotransduction Melanoma Phenotypes Plasticity siRNA Skin cancer Stem cells Tumorigenicity |
title | Geometric regulation of histone state directs melanoma reprogramming |
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