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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{
  "DOI": "10.1186/s13059-021-02339-6", 
  "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.", 
  "author": [
    {
      "family": "Huang", 
      "given": " Chia-Chi Flora"
    }, 
    {
      "family": "Lingadahalli", 
      "given": " Shreyas"
    }, 
    {
      "family": "Morova", 
      "given": " Tunc"
    }, 
    {
      "family": "Ozturan", 
      "given": " Dogancan"
    }, 
    {
      "family": "Hu", 
      "given": " Eugene"
    }, 
    {
      "family": "Yu", 
      "given": " Ivan Pak Lok"
    }, 
    {
      "family": "Linder", 
      "given": " Simon"
    }, 
    {
      "family": "Hoogstraat", 
      "given": " Marlous"
    }, 
    {
      "family": "Stelloo", 
      "given": " Suzan"
    }, 
    {
      "family": "Sar", 
      "given": " Funda"
    }, 
    {
      "family": "van der Poel", 
      "given": " Henk"
    }, 
    {
      "family": "Altintas", 
      "given": " Umut Berkay"
    }, 
    {
      "family": "Saffarzadeh", 
      "given": " Mohammadali"
    }, 
    {
      "family": "Le Bihan", 
      "given": " Stephane"
    }, 
    {
      "family": "McConeghy", 
      "given": " Brian"
    }, 
    {
      "family": "Gokbayrak", 
      "given": " Bengul"
    }, 
    {
      "family": "Feng", 
      "given": " Felix Y."
    }, 
    {
      "family": "Gleave", 
      "given": " Martin E."
    }, 
    {
      "family": "Bergman", 
      "given": " Andries M."
    }, 
    {
      "family": "Collins", 
      "given": " Colin"
    }, 
    {
      "family": "Collins", 
      "given": " Colin"
    }
  ], 
  "container_title": "GENOME BIOLOGY", 
  "id": "234974", 
  "issue": "1", 
  "issued": {
    "date-parts": [
      [
        2021, 
        1, 
        1
      ]
    ]
  }, 
  "title": "Functional mapping of androgen receptor enhancer activity", 
  "type": "article-journal", 
  "volume": "22"
}