---
res:
  bibo_abstract:
  - 'In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative
    mapping from promoter sequences to gene-expression levels that is compatible with
    in vivo and in vitro biophysical measurements. Such concordance has not been achieved
    for models of enhancer function in eukaryotes. In equilibrium models, it is difficult
    to reconcile the reported short transcription factor (TF) residence times on the
    DNA with the high specificity of regulation. In nonequilibrium models, progress
    is difficult due to an explosion in the number of parameters. Here, we navigate
    this complexity by looking for minimal nonequilibrium enhancer models that yield
    desired regulatory phenotypes: low TF residence time, high specificity, and tunable
    cooperativity. We find that a single extra parameter, interpretable as the “linking
    rate,” by which bound TFs interact with Mediator components, enables our models
    to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining
    consistent with the reported phenomenology and simple enough to be inferred from
    upcoming experiments. We further find that high specificity in nonequilibrium
    models is in a trade-off with gene-expression noise, predicting bursty dynamics—an
    experimentally observed hallmark of eukaryotic transcription. By drastically reducing
    the vast parameter space of nonequilibrium enhancer models to a much smaller subspace
    that optimally realizes biological function, we deliver a rich class of models
    that could be tractably inferred from data in the near future.@eng'
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Rok
      foaf_name: Grah, Rok
      foaf_surname: Grah
      foaf_workInfoHomepage: http://www.librecat.org/personId=483E70DE-F248-11E8-B48F-1D18A9856A87
    orcid: 0000-0003-2539-3560
  - foaf_Person:
      foaf_givenName: Benjamin
      foaf_name: Zoller, Benjamin
      foaf_surname: Zoller
  - foaf_Person:
      foaf_givenName: Gašper
      foaf_name: Tkačik, Gašper
      foaf_surname: Tkačik
      foaf_workInfoHomepage: http://www.librecat.org/personId=3D494DCA-F248-11E8-B48F-1D18A9856A87
    orcid: 0000-0002-6699-1455
  bibo_doi: 10.1073/pnas.2006731117
  bibo_issue: '50'
  bibo_volume: 117
  dct_date: 2020^xs_gYear
  dct_identifier:
  - UT:000600608300015
  dct_isPartOf:
  - http://id.crossref.org/issn/0027-8424
  - http://id.crossref.org/issn/1091-6490
  dct_language: eng
  dct_publisher: National Academy of Sciences@
  dct_title: Nonequilibrium models of optimal enhancer function@
  fabio_hasPubmedId: '33268497'
...
