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Functional mapping of androgen receptor enhancer activity

Huang, Chia-Chi Flora; Lingadahalli, Shreyas; Morova, Tunc; Ozturan, Dogancan; Hu, Eugene; Yu, Ivan Pak Lok; Linder, Simon; Hoogstraat, Marlous; Stelloo, Suzan; Sar, Funda; van der Poel, Henk; Altintas, Umut Berkay; Saffarzadeh, Mohammadali; Le Bihan, Stephane; McConeghy, Brian; Gokbayrak, Bengul; Feng, Felix Y.; Gleave, Martin E.; Bergman, Andries M.; Collins, Colin; Collins, Colin


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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/234974</identifier>
  <creators>
    <creator>
      <creatorName>Huang, Chia-Chi Flora</creatorName>
      <givenName>Chia-Chi Flora</givenName>
      <familyName>Huang</familyName>
      <affiliation>Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada</affiliation>
    </creator>
    <creator>
      <creatorName>Lingadahalli, Shreyas</creatorName>
      <givenName>Shreyas</givenName>
      <familyName>Lingadahalli</familyName>
      <affiliation>Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada</affiliation>
    </creator>
    <creator>
      <creatorName>Morova, Tunc</creatorName>
      <givenName>Tunc</givenName>
      <familyName>Morova</familyName>
      <affiliation>Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada</affiliation>
    </creator>
    <creator>
      <creatorName>Ozturan, Dogancan</creatorName>
      <givenName>Dogancan</givenName>
      <familyName>Ozturan</familyName>
    </creator>
    <creator>
      <creatorName>Hu, Eugene</creatorName>
      <givenName>Eugene</givenName>
      <familyName>Hu</familyName>
      <affiliation>Simon Fraser Univ, Dept Phys, Burnaby, BC, Canada</affiliation>
    </creator>
    <creator>
      <creatorName>Yu, Ivan Pak Lok</creatorName>
      <givenName>Ivan Pak Lok</givenName>
      <familyName>Yu</familyName>
      <affiliation>Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada</affiliation>
    </creator>
    <creator>
      <creatorName>Linder, Simon</creatorName>
      <givenName>Simon</givenName>
      <familyName>Linder</familyName>
      <affiliation>Netherlands Canc Inst, Oncode Inst, Div Oncogen, Amsterdam, Netherlands</affiliation>
    </creator>
    <creator>
      <creatorName>Hoogstraat, Marlous</creatorName>
      <givenName>Marlous</givenName>
      <familyName>Hoogstraat</familyName>
    </creator>
    <creator>
      <creatorName>Stelloo, Suzan</creatorName>
      <givenName>Suzan</givenName>
      <familyName>Stelloo</familyName>
      <affiliation>Netherlands Canc Inst, Oncode Inst, Div Oncogen, Amsterdam, Netherlands</affiliation>
    </creator>
    <creator>
      <creatorName>Sar, Funda</creatorName>
      <givenName>Funda</givenName>
      <familyName>Sar</familyName>
      <affiliation>Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada</affiliation>
    </creator>
    <creator>
      <creatorName>van der Poel, Henk</creatorName>
      <givenName>Henk</givenName>
      <familyName>van der Poel</familyName>
      <affiliation>Netherlands Canc Inst, Div Urol, Amsterdam, Netherlands</affiliation>
    </creator>
    <creator>
      <creatorName>Altintas, Umut Berkay</creatorName>
      <givenName>Umut Berkay</givenName>
      <familyName>Altintas</familyName>
    </creator>
    <creator>
      <creatorName>Saffarzadeh, Mohammadali</creatorName>
      <givenName>Mohammadali</givenName>
      <familyName>Saffarzadeh</familyName>
      <affiliation>Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada</affiliation>
    </creator>
    <creator>
      <creatorName>Le Bihan, Stephane</creatorName>
      <givenName>Stephane</givenName>
      <familyName>Le Bihan</familyName>
      <affiliation>Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada</affiliation>
    </creator>
    <creator>
      <creatorName>McConeghy, Brian</creatorName>
      <givenName>Brian</givenName>
      <familyName>McConeghy</familyName>
      <affiliation>Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada</affiliation>
    </creator>
    <creator>
      <creatorName>Gokbayrak, Bengul</creatorName>
      <givenName>Bengul</givenName>
      <familyName>Gokbayrak</familyName>
    </creator>
    <creator>
      <creatorName>Feng, Felix Y.</creatorName>
      <givenName>Felix Y.</givenName>
      <familyName>Feng</familyName>
      <affiliation>Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA</affiliation>
    </creator>
    <creator>
      <creatorName>Gleave, Martin E.</creatorName>
      <givenName>Martin E.</givenName>
      <familyName>Gleave</familyName>
      <affiliation>Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada</affiliation>
    </creator>
    <creator>
      <creatorName>Bergman, Andries M.</creatorName>
      <givenName>Andries M.</givenName>
      <familyName>Bergman</familyName>
    </creator>
    <creator>
      <creatorName>Collins, Colin</creatorName>
      <givenName>Colin</givenName>
      <familyName>Collins</familyName>
      <affiliation>Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada</affiliation>
    </creator>
    <creator>
      <creatorName>Collins, Colin</creatorName>
      <givenName>Colin</givenName>
      <familyName>Collins</familyName>
      <affiliation>Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Functional Mapping Of Androgen Receptor Enhancer Activity</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2021</publicationYear>
  <dates>
    <date dateType="Issued">2021-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/234974</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1186/s13059-021-02339-6</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">Background Androgen receptor (AR) is critical to the initiation, growth, and progression of prostate cancer. Once activated, the AR binds to cis-regulatory enhancer elements on DNA that drive gene expression. Yet, there are 10-100x more binding sites than differentially expressed genes. It is unclear how or if these excess binding sites impact gene transcription. Results To characterize the regulatory logic of AR-mediated transcription, we generated a locus-specific map of enhancer activity by functionally testing all common clinical AR binding sites with Self-Transcribing Active Regulatory Regions sequencing (STARRseq). Only 7% of AR binding sites displayed androgen-dependent enhancer activity. Instead, the vast majority of AR binding sites were either inactive or constitutively active enhancers. These annotations strongly correlated with enhancer-associated features of both in vitro cell lines and clinical prostate cancer samples. Evaluating the effect of each enhancer class on transcription, we found that AR-regulated enhancers frequently interact with promoters and form central chromosomal loops that are required for transcription. Somatic mutations of these critical AR-regulated enhancers often impact enhancer activity. Conclusions Using a functional map of AR enhancer activity, we demonstrated that AR-regulated enhancers act as a regulatory hub that increases interactions with other AR binding sites and gene promoters.</description>
  </descriptions>
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