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An extended transcription factor regulatory network controls hepatocyte identity

Julie Dubois-Chevalier, Celine Gheeraert, Alexandre Berthier, Clemence Boulet, Vanessa Dubois (UGent) , Loic Guille, Marie Fourcot, Guillemette Marot, Karine Gauthier, Laurent Dubuquoy, et al.
(2023) EMBO REPORTS. 24(9).
Author
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Abstract
Cell identity is specified by a core transcriptional regulatory circuitry (CoRC), typically limited to a small set of interconnected cell-specific transcription factors (TFs). By mining global hepatic TF regulons, we reveal a more complex organization of the transcriptional regulatory network controlling hepatocyte identity. We show that tight functional interconnections controlling hepatocyte identity extend to non-cell-specific TFs beyond the CoRC, which we call hepatocyte identity (Hep-ID)(CONNECT) TFs. Besides controlling identity effector genes, Hep-IDCONNECT TFs also engage in reciprocal transcriptional regulation with TFs of the CoRC. In homeostatic basal conditions, this translates into Hep-IDCONNECT TFs being involved in fine tuning CoRC TF expression including their rhythmic expression patterns. Moreover, a role for Hep-IDCONNECT TFs in the control of hepatocyte identity is revealed in dedifferentiated hepatocytes where Hep-IDCONNECT TFs are able to reset CoRC TF expression. This is observed upon activation of NR1H3 or THRB in hepatocarcinoma or in hepatocytes subjected to inflammation-induced loss of identity. Our study establishes that hepatocyte identity is controlled by an extended array of TFs beyond the CoRC.
Keywords
transcription factors, liver disease, hepatocyte dedifferentiation, core regulatory network, cell identity

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MLA
Dubois-Chevalier, Julie, et al. “An Extended Transcription Factor Regulatory Network Controls Hepatocyte Identity.” EMBO REPORTS, vol. 24, no. 9, 2023, doi:10.15252/embr.202357020.
APA
Dubois-Chevalier, J., Gheeraert, C., Berthier, A., Boulet, C., Dubois, V., Guille, L., … Eeckhoute, J. (2023). An extended transcription factor regulatory network controls hepatocyte identity. EMBO REPORTS, 24(9). https://doi.org/10.15252/embr.202357020
Chicago author-date
Dubois-Chevalier, Julie, Celine Gheeraert, Alexandre Berthier, Clemence Boulet, Vanessa Dubois, Loic Guille, Marie Fourcot, et al. 2023. “An Extended Transcription Factor Regulatory Network Controls Hepatocyte Identity.” EMBO REPORTS 24 (9). https://doi.org/10.15252/embr.202357020.
Chicago author-date (all authors)
Dubois-Chevalier, Julie, Celine Gheeraert, Alexandre Berthier, Clemence Boulet, Vanessa Dubois, Loic Guille, Marie Fourcot, Guillemette Marot, Karine Gauthier, Laurent Dubuquoy, Bart Staels, Philippe Lefebvre, and Jerome Eeckhoute. 2023. “An Extended Transcription Factor Regulatory Network Controls Hepatocyte Identity.” EMBO REPORTS 24 (9). doi:10.15252/embr.202357020.
Vancouver
1.
Dubois-Chevalier J, Gheeraert C, Berthier A, Boulet C, Dubois V, Guille L, et al. An extended transcription factor regulatory network controls hepatocyte identity. EMBO REPORTS. 2023;24(9).
IEEE
[1]
J. Dubois-Chevalier et al., “An extended transcription factor regulatory network controls hepatocyte identity,” EMBO REPORTS, vol. 24, no. 9, 2023.
@article{01HAC0G70411AWWTT7PBSS1TZ8,
  abstract     = {{Cell identity is specified by a core transcriptional regulatory circuitry (CoRC), typically limited to a small set of interconnected cell-specific transcription factors (TFs). By mining global hepatic TF regulons, we reveal a more complex organization of the transcriptional regulatory network controlling hepatocyte identity. We show that tight functional interconnections controlling hepatocyte identity extend to non-cell-specific TFs beyond the CoRC, which we call hepatocyte identity (Hep-ID)(CONNECT) TFs. Besides controlling identity effector genes, Hep-IDCONNECT TFs also engage in reciprocal transcriptional regulation with TFs of the CoRC. In homeostatic basal conditions, this translates into Hep-IDCONNECT TFs being involved in fine tuning CoRC TF expression including their rhythmic expression patterns. Moreover, a role for Hep-IDCONNECT TFs in the control of hepatocyte identity is revealed in dedifferentiated hepatocytes where Hep-IDCONNECT TFs are able to reset CoRC TF expression. This is observed upon activation of NR1H3 or THRB in hepatocarcinoma or in hepatocytes subjected to inflammation-induced loss of identity. Our study establishes that hepatocyte identity is controlled by an extended array of TFs beyond the CoRC.}},
  articleno    = {{e57020}},
  author       = {{Dubois-Chevalier, Julie and  Gheeraert, Celine and  Berthier, Alexandre and  Boulet, Clemence and Dubois, Vanessa and  Guille, Loic and  Fourcot, Marie and  Marot, Guillemette and  Gauthier, Karine and  Dubuquoy, Laurent and  Staels, Bart and Lefebvre, Philippe and Eeckhoute, Jerome}},
  issn         = {{1469-221X}},
  journal      = {{EMBO REPORTS}},
  keywords     = {{transcription factors,liver disease,hepatocyte dedifferentiation,core regulatory network,cell identity}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{18}},
  title        = {{An extended transcription factor regulatory network controls hepatocyte identity}},
  url          = {{http://doi.org/10.15252/embr.202357020}},
  volume       = {{24}},
  year         = {{2023}},
}
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