A SNAI2/CTCF Interaction is Required for NOTCH1 Expression in Rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is a pediatric malignancy of the muscle with characteristics of cells blocked in differentiation. is an oncogene that promotes self-renewal and blocks differentiation in the fusion negative-RMS sub-type. However, how expression is transcriptionally maintained in tumors is unkn...
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| Veröffentlicht in: | Molecular and cellular biology 2023, Vol.43 (11), p.547-565 |
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| creator | Sreenivas, Prethish Wang, Long Wang, Meng Challa, Anil Modi, Paulomi Hensch, Nicole Rae Gryder, Berkley Chou, Hsien-Chao Zhao, Xiang R Sunkel, Benjamin Moreno-Campos, Rodrigo Khan, Javed Stanton, Benjamin Z Ignatius, Myron S |
| description | Rhabdomyosarcoma (RMS) is a pediatric malignancy of the muscle with characteristics of cells blocked in differentiation.
is an oncogene that promotes self-renewal and blocks differentiation in the fusion negative-RMS sub-type. However, how
expression is transcriptionally maintained in tumors is unknown. Analyses of SNAI2 and CTCF chromatin binding and HiC analyses revealed a conserved SNAI2/CTCF overlapping peak downstream of the
locus marking a sub-topologically associating domain (TAD) boundary. Deletion of the SNAI2-CTCF peak showed that it is essential for
expression and viability of FN-RMS cells. Reintroducing constitutively activated
-ΔE in cells with the SNAI2-CTCF peak deleted restored cell-viability. Ablation of SNAI2 using CRISPR/Cas9 reagents resulted in the loss of majority of RD and SMS-CTR FN-RMS cells. However, the few surviving clones that repopulate cultures have recovered
. Cells that re-establish
expression after SNAI2 ablation are unable to differentiate robustly as SNAI2 shRNA knockdown cells; yet,
-ablated cells continued to be exquisitely sensitive to ionizing radiation. Thus, we have uncovered a novel mechanism by which SNAI2 and CTCF maintenance of a sub-TAD boundary promotes rather than represses
expression. Further, we demonstrate that SNAI2 suppression of apoptosis post-radiation is independent of
/
effects on self-renewal and differentiation. |
| doi_str_mv | 10.1080/10985549.2023.2256640 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10761179</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2882325619</sourcerecordid><originalsourceid>FETCH-LOGICAL-c360t-514c2292513c1e30c7e9a60f9c7c39b1c1d1b05653daf2d930a5e30df0fcdcbf3</originalsourceid><addsrcrecordid>eNpVUV1PwjAUbYxGEP0Jmj36Mrht6UafDCGgJAQSxOem61qZYSu0m5F_7yYfwad7c-85596cg9Ajhi6GAfQw8AFjfd4lQGiXEBZFfbhC7WYeNovri76F7rz_AoCIA71FLRoPBgSifhvNh8H7fDglvdFqNAmmRamdVGVmiyDzwVLvqszpNDDWBfPFavSGg_HP1mnv_xBFsFzLJLX53nrplM3lPboxcuP1w7F20MdkXPPC2eJ1OhrOQkUjKEOG-4oQThimCmsKKtZcRmC4ihXlCVY4xQmwiNFUGpJyCpLVsNSAUalKDO2gl4PutkpynSpdlE5uxNZluXR7YWUm_m-KbC0-7bfAEEcYx7xWeD4qOLurtC9FnnmlNxtZaFt5QWqHaO0qbqDsAFXOeu-0Od_BIJowxCkM0YQhjmHUvKfLJ8-sk_v0F8ZJhIg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2882325619</pqid></control><display><type>article</type><title>A SNAI2/CTCF Interaction is Required for NOTCH1 Expression in Rhabdomyosarcoma</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Sreenivas, Prethish ; Wang, Long ; Wang, Meng ; Challa, Anil ; Modi, Paulomi ; Hensch, Nicole Rae ; Gryder, Berkley ; Chou, Hsien-Chao ; Zhao, Xiang R ; Sunkel, Benjamin ; Moreno-Campos, Rodrigo ; Khan, Javed ; Stanton, Benjamin Z ; Ignatius, Myron S</creator><creatorcontrib>Sreenivas, Prethish ; Wang, Long ; Wang, Meng ; Challa, Anil ; Modi, Paulomi ; Hensch, Nicole Rae ; Gryder, Berkley ; Chou, Hsien-Chao ; Zhao, Xiang R ; Sunkel, Benjamin ; Moreno-Campos, Rodrigo ; Khan, Javed ; Stanton, Benjamin Z ; Ignatius, Myron S</creatorcontrib><description>Rhabdomyosarcoma (RMS) is a pediatric malignancy of the muscle with characteristics of cells blocked in differentiation.
is an oncogene that promotes self-renewal and blocks differentiation in the fusion negative-RMS sub-type. However, how
expression is transcriptionally maintained in tumors is unknown. Analyses of SNAI2 and CTCF chromatin binding and HiC analyses revealed a conserved SNAI2/CTCF overlapping peak downstream of the
locus marking a sub-topologically associating domain (TAD) boundary. Deletion of the SNAI2-CTCF peak showed that it is essential for
expression and viability of FN-RMS cells. Reintroducing constitutively activated
-ΔE in cells with the SNAI2-CTCF peak deleted restored cell-viability. Ablation of SNAI2 using CRISPR/Cas9 reagents resulted in the loss of majority of RD and SMS-CTR FN-RMS cells. However, the few surviving clones that repopulate cultures have recovered
. Cells that re-establish
expression after SNAI2 ablation are unable to differentiate robustly as SNAI2 shRNA knockdown cells; yet,
-ablated cells continued to be exquisitely sensitive to ionizing radiation. Thus, we have uncovered a novel mechanism by which SNAI2 and CTCF maintenance of a sub-TAD boundary promotes rather than represses
expression. Further, we demonstrate that SNAI2 suppression of apoptosis post-radiation is independent of
/
effects on self-renewal and differentiation.</description><identifier>ISSN: 1098-5549</identifier><identifier>ISSN: 0270-7306</identifier><identifier>EISSN: 1098-5549</identifier><identifier>DOI: 10.1080/10985549.2023.2256640</identifier><identifier>PMID: 37882064</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>CCCTC-Binding Factor - metabolism ; Child ; Chromatin ; Genetics and Molecular Biology ; Humans ; Receptor, Notch1 - genetics ; Receptor, Notch1 - metabolism ; Rhabdomyosarcoma - genetics ; RNA, Small Interfering - genetics ; Snail Family Transcription Factors - genetics ; Snail Family Transcription Factors - metabolism</subject><ispartof>Molecular and cellular biology, 2023, Vol.43 (11), p.547-565</ispartof><rights>2023 The Author(s). Published with license by Taylor & Francis Group, LLC. 2023 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c360t-514c2292513c1e30c7e9a60f9c7c39b1c1d1b05653daf2d930a5e30df0fcdcbf3</cites><orcidid>0000-0002-1260-4464 ; 0000-0001-6639-7707</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/PMC10761179/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761179/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37882064$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sreenivas, Prethish</creatorcontrib><creatorcontrib>Wang, Long</creatorcontrib><creatorcontrib>Wang, Meng</creatorcontrib><creatorcontrib>Challa, Anil</creatorcontrib><creatorcontrib>Modi, Paulomi</creatorcontrib><creatorcontrib>Hensch, Nicole Rae</creatorcontrib><creatorcontrib>Gryder, Berkley</creatorcontrib><creatorcontrib>Chou, Hsien-Chao</creatorcontrib><creatorcontrib>Zhao, Xiang R</creatorcontrib><creatorcontrib>Sunkel, Benjamin</creatorcontrib><creatorcontrib>Moreno-Campos, Rodrigo</creatorcontrib><creatorcontrib>Khan, Javed</creatorcontrib><creatorcontrib>Stanton, Benjamin Z</creatorcontrib><creatorcontrib>Ignatius, Myron S</creatorcontrib><title>A SNAI2/CTCF Interaction is Required for NOTCH1 Expression in Rhabdomyosarcoma</title><title>Molecular and cellular biology</title><addtitle>Mol Cell Biol</addtitle><description>Rhabdomyosarcoma (RMS) is a pediatric malignancy of the muscle with characteristics of cells blocked in differentiation.
is an oncogene that promotes self-renewal and blocks differentiation in the fusion negative-RMS sub-type. However, how
expression is transcriptionally maintained in tumors is unknown. Analyses of SNAI2 and CTCF chromatin binding and HiC analyses revealed a conserved SNAI2/CTCF overlapping peak downstream of the
locus marking a sub-topologically associating domain (TAD) boundary. Deletion of the SNAI2-CTCF peak showed that it is essential for
expression and viability of FN-RMS cells. Reintroducing constitutively activated
-ΔE in cells with the SNAI2-CTCF peak deleted restored cell-viability. Ablation of SNAI2 using CRISPR/Cas9 reagents resulted in the loss of majority of RD and SMS-CTR FN-RMS cells. However, the few surviving clones that repopulate cultures have recovered
. Cells that re-establish
expression after SNAI2 ablation are unable to differentiate robustly as SNAI2 shRNA knockdown cells; yet,
-ablated cells continued to be exquisitely sensitive to ionizing radiation. Thus, we have uncovered a novel mechanism by which SNAI2 and CTCF maintenance of a sub-TAD boundary promotes rather than represses
expression. Further, we demonstrate that SNAI2 suppression of apoptosis post-radiation is independent of
/
effects on self-renewal and differentiation.</description><subject>CCCTC-Binding Factor - metabolism</subject><subject>Child</subject><subject>Chromatin</subject><subject>Genetics and Molecular Biology</subject><subject>Humans</subject><subject>Receptor, Notch1 - genetics</subject><subject>Receptor, Notch1 - metabolism</subject><subject>Rhabdomyosarcoma - genetics</subject><subject>RNA, Small Interfering - genetics</subject><subject>Snail Family Transcription Factors - genetics</subject><subject>Snail Family Transcription Factors - metabolism</subject><issn>1098-5549</issn><issn>0270-7306</issn><issn>1098-5549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUV1PwjAUbYxGEP0Jmj36Mrht6UafDCGgJAQSxOem61qZYSu0m5F_7yYfwad7c-85596cg9Ajhi6GAfQw8AFjfd4lQGiXEBZFfbhC7WYeNovri76F7rz_AoCIA71FLRoPBgSifhvNh8H7fDglvdFqNAmmRamdVGVmiyDzwVLvqszpNDDWBfPFavSGg_HP1mnv_xBFsFzLJLX53nrplM3lPboxcuP1w7F20MdkXPPC2eJ1OhrOQkUjKEOG-4oQThimCmsKKtZcRmC4ihXlCVY4xQmwiNFUGpJyCpLVsNSAUalKDO2gl4PutkpynSpdlE5uxNZluXR7YWUm_m-KbC0-7bfAEEcYx7xWeD4qOLurtC9FnnmlNxtZaFt5QWqHaO0qbqDsAFXOeu-0Od_BIJowxCkM0YQhjmHUvKfLJ8-sk_v0F8ZJhIg</recordid><startdate>2023</startdate><enddate>2023</enddate><creator>Sreenivas, Prethish</creator><creator>Wang, Long</creator><creator>Wang, Meng</creator><creator>Challa, Anil</creator><creator>Modi, Paulomi</creator><creator>Hensch, Nicole Rae</creator><creator>Gryder, Berkley</creator><creator>Chou, Hsien-Chao</creator><creator>Zhao, Xiang R</creator><creator>Sunkel, Benjamin</creator><creator>Moreno-Campos, Rodrigo</creator><creator>Khan, Javed</creator><creator>Stanton, Benjamin Z</creator><creator>Ignatius, Myron S</creator><general>Taylor & Francis</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1260-4464</orcidid><orcidid>https://orcid.org/0000-0001-6639-7707</orcidid></search><sort><creationdate>2023</creationdate><title>A SNAI2/CTCF Interaction is Required for NOTCH1 Expression in Rhabdomyosarcoma</title><author>Sreenivas, Prethish ; Wang, Long ; Wang, Meng ; Challa, Anil ; Modi, Paulomi ; Hensch, Nicole Rae ; Gryder, Berkley ; Chou, Hsien-Chao ; Zhao, Xiang R ; Sunkel, Benjamin ; Moreno-Campos, Rodrigo ; Khan, Javed ; Stanton, Benjamin Z ; Ignatius, Myron S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c360t-514c2292513c1e30c7e9a60f9c7c39b1c1d1b05653daf2d930a5e30df0fcdcbf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>CCCTC-Binding Factor - metabolism</topic><topic>Child</topic><topic>Chromatin</topic><topic>Genetics and Molecular Biology</topic><topic>Humans</topic><topic>Receptor, Notch1 - genetics</topic><topic>Receptor, Notch1 - metabolism</topic><topic>Rhabdomyosarcoma - genetics</topic><topic>RNA, Small Interfering - genetics</topic><topic>Snail Family Transcription Factors - genetics</topic><topic>Snail Family Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sreenivas, Prethish</creatorcontrib><creatorcontrib>Wang, Long</creatorcontrib><creatorcontrib>Wang, Meng</creatorcontrib><creatorcontrib>Challa, Anil</creatorcontrib><creatorcontrib>Modi, Paulomi</creatorcontrib><creatorcontrib>Hensch, Nicole Rae</creatorcontrib><creatorcontrib>Gryder, Berkley</creatorcontrib><creatorcontrib>Chou, Hsien-Chao</creatorcontrib><creatorcontrib>Zhao, Xiang R</creatorcontrib><creatorcontrib>Sunkel, Benjamin</creatorcontrib><creatorcontrib>Moreno-Campos, Rodrigo</creatorcontrib><creatorcontrib>Khan, Javed</creatorcontrib><creatorcontrib>Stanton, Benjamin Z</creatorcontrib><creatorcontrib>Ignatius, Myron S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular and cellular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sreenivas, Prethish</au><au>Wang, Long</au><au>Wang, Meng</au><au>Challa, Anil</au><au>Modi, Paulomi</au><au>Hensch, Nicole Rae</au><au>Gryder, Berkley</au><au>Chou, Hsien-Chao</au><au>Zhao, Xiang R</au><au>Sunkel, Benjamin</au><au>Moreno-Campos, Rodrigo</au><au>Khan, Javed</au><au>Stanton, Benjamin Z</au><au>Ignatius, Myron S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A SNAI2/CTCF Interaction is Required for NOTCH1 Expression in Rhabdomyosarcoma</atitle><jtitle>Molecular and cellular biology</jtitle><addtitle>Mol Cell Biol</addtitle><date>2023</date><risdate>2023</risdate><volume>43</volume><issue>11</issue><spage>547</spage><epage>565</epage><pages>547-565</pages><issn>1098-5549</issn><issn>0270-7306</issn><eissn>1098-5549</eissn><abstract>Rhabdomyosarcoma (RMS) is a pediatric malignancy of the muscle with characteristics of cells blocked in differentiation.
is an oncogene that promotes self-renewal and blocks differentiation in the fusion negative-RMS sub-type. However, how
expression is transcriptionally maintained in tumors is unknown. Analyses of SNAI2 and CTCF chromatin binding and HiC analyses revealed a conserved SNAI2/CTCF overlapping peak downstream of the
locus marking a sub-topologically associating domain (TAD) boundary. Deletion of the SNAI2-CTCF peak showed that it is essential for
expression and viability of FN-RMS cells. Reintroducing constitutively activated
-ΔE in cells with the SNAI2-CTCF peak deleted restored cell-viability. Ablation of SNAI2 using CRISPR/Cas9 reagents resulted in the loss of majority of RD and SMS-CTR FN-RMS cells. However, the few surviving clones that repopulate cultures have recovered
. Cells that re-establish
expression after SNAI2 ablation are unable to differentiate robustly as SNAI2 shRNA knockdown cells; yet,
-ablated cells continued to be exquisitely sensitive to ionizing radiation. Thus, we have uncovered a novel mechanism by which SNAI2 and CTCF maintenance of a sub-TAD boundary promotes rather than represses
expression. Further, we demonstrate that SNAI2 suppression of apoptosis post-radiation is independent of
/
effects on self-renewal and differentiation.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>37882064</pmid><doi>10.1080/10985549.2023.2256640</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0002-1260-4464</orcidid><orcidid>https://orcid.org/0000-0001-6639-7707</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular and cellular biology, 2023, Vol.43 (11), p.547-565 |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | CCCTC-Binding Factor - metabolism Child Chromatin Genetics and Molecular Biology Humans Receptor, Notch1 - genetics Receptor, Notch1 - metabolism Rhabdomyosarcoma - genetics RNA, Small Interfering - genetics Snail Family Transcription Factors - genetics Snail Family Transcription Factors - metabolism |
| title | A SNAI2/CTCF Interaction is Required for NOTCH1 Expression in Rhabdomyosarcoma |
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