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+<table><tbody><tr><td><table cellpadding="2" cellspacing="0" width="600"><tbody><tr bgcolor="#cccccc" valign="top"><td colspan="2"><table width="600"><tbody><tr><td><strong class="acc" id="GSE279335"><a href="/geo/query/acc.cgi?acc=GSE279335" onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_recenter)">Series GSE279335</a></strong></td>
+<td></td>
+<td align="right" onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_gds)"><a href="/gds/?term=GSE279335[Accession]">Query DataSets for GSE279335</a></td>
+</tr></tbody></table></td></tr>
+<tr valign="top"><td>Status</td>
+<td>Public on Oct 25, 2024</td>
+</tr>
+<tr valign="top"><td nowrap="">Title</td>
+<td style="text-align: justify">Dependence of PAX3-FOXO1 chromatin occupancy on ETS1 at important disease-promoting genes exposes new targetable vulnerability in Fusion-Positive Rhabdomyosarcoma [RNA-Seq]</td>
+</tr>
+<tr valign="top"><td nowrap="">Organism</td>
+<td><a href="/Taxonomy/Browser/wwwtax.cgi?mode=Info&amp;id=9606" onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_organismus)">Homo sapiens</a></td>
+</tr>
+<tr valign="top"><td nowrap="">Experiment type</td>
+<td>Expression profiling by high throughput sequencing<br></td>
+</tr>
+<tr valign="top"><td nowrap="">Summary</td>
+<td style="text-align: justify">Rhabdomyosarcoma (RMS), a malignancy of impaired myogenic differentiation, is the most common soft tissue pediatric cancer. PAX3-FOXO1 oncofusions drive the majority of the clinically more aggressive fusion-positive rhabdomyosarcoma (FP-RMS). Recent studies have established an epigenetic basis for PAX3-FOXO1-driven oncogenic processes. However, details of PAX3-FOXO1 epigenetic mechanisms, including interactions with, and dependence on, other chromatin and transcription factors, are incompletely understood. We previously identified a novel disease-promoting epigenetic axis in RMS, involving the histone demethylase KDM3A and the ETS1 transcription factor, and demonstrated that this epigenetic axis interfaces with PAX3-FOXO1 both phenotypically and transcriptomically, including co-regulation of biological processes and genes important to FP-RMS progression. In this study, we demonstrate that KDM3A and ETS1 colocalize with PAX3-FOXO1 to enhancers of important disease-promoting genes in FP-RMS, including FGF8, IL4R, and MEST, as well as PODXL, which we define herein as a new FP-RMS-promoting gene. We show that ETS1, which is induced by both PAX3-FOXO1 and KDM3A, exists in complex with PAX3-FOXO1, and augments PAX3-FOXO1 chromatin occupancy. We further show that the PAX3-FOXO1/ETS1 complex can be disrupted by the clinically relevant small molecule inhibitor YK-4-279. YK-4-279 displaces PAX3-FOXO1 from chromatin and interferes with PAX3-FOXO1-dependent gene regulation, resulting in potent inhibition of growth and invasive properties in FP-RMS, along with downregulation of FGF8, IL4R, MEST and PODXL expression. We additionally show that, in some FP-RMS, KDM3A also increases PAX3-FOXO1 levels. Together, our studies illuminate mechanisms of action of the KDM3A/ETS1 regulatory module, and reveal novel targetable mechanisms of PAX3-FOXO1 chromatin complex regulation, in FP-RMS.<br></td>
+</tr>
+<tr valign="top"><td nowrap="">&nbsp;</td>
+<td></td>
+</tr>
+<tr valign="top"><td nowrap="">Overall design</td>
+<td style="text-align: justify">RNAseq was used to compare the effects of YK-4-279, relative to vehicle control, on gene expression in FP-RMS cells.<br></td>
+</tr>
+<tr valign="top"><td nowrap="">&nbsp;</td>
+<td></td>
+</tr>
+<tr valign="top"><td>Contributor(s)</td>
+<td><a href="/pubmed/?term=Jedlicka P[Author]">Jedlicka P</a>, <a href="/pubmed/?term=Hsieh J[Author]">Hsieh J</a>, <a href="/pubmed/?term=Danis E[Author]">Danis E</a>, <a href="/pubmed/?term=Owens CR[Author]">Owens CR</a>, <a href="/pubmed/?term=Parrish JK[Author]">Parrish JK</a>, <a href="/pubmed/?term=Nowling NL[Author]">Nowling NL</a>, <a href="/pubmed/?term=Wolin AR[Author]">Wolin AR</a>, <a href="/pubmed/?term=Purdy S[Author]">Purdy S</a>, <a href="/pubmed/?term=Rosenbaum SR[Author]">Rosenbaum SR</a>, <a href="/pubmed/?term=Ivancevic AM[Author]">Ivancevic AM</a>, <a href="/pubmed/?term=Chuong EB[Author]">Chuong EB</a>, <a href="/pubmed/?term=Ford HL[Author]">Ford HL</a></td>
+</tr>
+<tr valign="top"><td nowrap="">Citation(s)</td>
+<td><span class="pubmed_id" id="39448867"><!--?xml version="1.0" encoding="UTF-8"?-->
+<div class="PubmedCitation"><ul><li><span class="authors">Hsieh J, Danis EP, Owens CR, Parrish JK et al. </span><span class="title">Dependence of PAX3-FOXO1 chromatin occupancy on ETS1 at important disease-promoting genes exposes new targetable vulnerability in Fusion-Positive Rhabdomyosarcoma. </span><span class="source">Oncogene</span> 2025 Jan;44(1):19-29. PMID:&nbsp;<a title="Link to PubMed record" href="https://www.ncbi.nlm.nih.gov/pubmed/39448867">39448867</a></li></ul></div>
+</span></td>
+</tr>
+<tr valign="top"><td colspan="2"><span id="geo2r"></span> <span id="rnaseq_counts"></span></td></tr>
+<tr bgcolor="#eeeeee" valign="top"><td>Submission date</td>
+<td>Oct 11, 2024</td>
+</tr>
+<tr bgcolor="#eeeeee" valign="top"><td>Last update date</td>
+<td>Feb 12, 2025</td>
+</tr>
+<tr bgcolor="#eeeeee" valign="top"><td>Contact name</td>
+<td>Etienne Danis</td>
+</tr>
+<tr bgcolor="#eeeeee" valign="top"><td nowrap="">E-mail(s)</td>
+<td><a href="mailto:ETIENNE.DANIS@CUANSCHUTZ.EDU">ETIENNE.DANIS@CUANSCHUTZ.EDU</a><br></td>
+</tr>
+<tr bgcolor="#eeeeee" valign="top"><td nowrap="">Organization name</td>
+<td style="text-align: justify">University of Colorado, Denver - Anschutz Medical Campus<br></td>
+</tr>
+<tr bgcolor="#eeeeee" valign="top"><td nowrap="">Department</td>
+<td style="text-align: justify">Cancer Center<br></td>
+</tr>
+<tr bgcolor="#eeeeee" valign="top"><td nowrap="">Street address</td>
+<td style="text-align: justify">13001 E 17th Pl<br></td>
+</tr>
+<tr bgcolor="#eeeeee" valign="top"><td nowrap="">City</td>
+<td style="text-align: justify">AURORA</td>
+</tr>
+<tr bgcolor="#eeeeee" valign="top"><td nowrap="">State/province</td>
+<td style="text-align: justify">CO</td>
+</tr>
+<tr bgcolor="#eeeeee" valign="top"><td nowrap="">ZIP/Postal code</td>
+<td style="text-align: justify">80045</td>
+</tr>
+<tr bgcolor="#eeeeee" valign="top"><td nowrap="">Country</td>
+<td style="text-align: justify">USA</td>
+</tr>
+<tr valign="top"><td nowrap="">&nbsp;</td>
+<td></td>
+</tr>
+<tr valign="top"><td>Platforms (1)</td>
+<td onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_recenter)"><table cellpadding="3" style="position:relative;top:-5px;left:-5px"><tbody><tr><td valign="top"><a href="/geo/query/acc.cgi?acc=GPL24676" onmouseout="onLinkOut('HelpMessage' , geo_empty_help)" onmouseover="onLinkOver('HelpMessage' , geoaxema_recenter)">GPL24676</a></td>
+<td valign="top">Illumina NovaSeq 6000 (Homo sapiens)</td>
+</tr></tbody></table></td>
+</tr>
+</td></tr></tbody></table>
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