1 Ocak 2021 Dergi makalesi Açık Erişim

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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{
  "@context": "https://schema.org/", 
  "@id": 234974, 
  "@type": "ScholarlyArticle", 
  "creator": [
    {
      "@type": "Person", 
      "affiliation": "Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada", 
      "name": "Huang, Chia-Chi Flora"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada", 
      "name": "Lingadahalli, Shreyas"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada", 
      "name": "Morova, Tunc"
    }, 
    {
      "@type": "Person", 
      "name": "Ozturan, Dogancan"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Simon Fraser Univ, Dept Phys, Burnaby, BC, Canada", 
      "name": "Hu, Eugene"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada", 
      "name": "Yu, Ivan Pak Lok"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Netherlands Canc Inst, Oncode Inst, Div Oncogen, Amsterdam, Netherlands", 
      "name": "Linder, Simon"
    }, 
    {
      "@type": "Person", 
      "name": "Hoogstraat, Marlous"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Netherlands Canc Inst, Oncode Inst, Div Oncogen, Amsterdam, Netherlands", 
      "name": "Stelloo, Suzan"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada", 
      "name": "Sar, Funda"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Netherlands Canc Inst, Div Urol, Amsterdam, Netherlands", 
      "name": "van der Poel, Henk"
    }, 
    {
      "@type": "Person", 
      "name": "Altintas, Umut Berkay"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada", 
      "name": "Saffarzadeh, Mohammadali"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada", 
      "name": "Le Bihan, Stephane"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada", 
      "name": "McConeghy, Brian"
    }, 
    {
      "@type": "Person", 
      "name": "Gokbayrak, Bengul"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA", 
      "name": "Feng, Felix Y."
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada", 
      "name": "Gleave, Martin E."
    }, 
    {
      "@type": "Person", 
      "name": "Bergman, Andries M."
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada", 
      "name": "Collins, Colin"
    }, 
    {
      "@type": "Person", 
      "affiliation": "Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada", 
      "name": "Collins, Colin"
    }
  ], 
  "datePublished": "2021-01-01", 
  "description": "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.", 
  "headline": "Functional mapping of androgen receptor enhancer activity", 
  "identifier": 234974, 
  "image": "https://aperta.ulakbim.gov.tr/static/img/logo/aperta_logo_with_icon.svg", 
  "license": "http://www.opendefinition.org/licenses/cc-by", 
  "name": "Functional mapping of androgen receptor enhancer activity", 
  "url": "https://aperta.ulakbim.gov.tr/record/234974"
}