| First Author | Dubois-Chevalier J | Year | 2023 |
| Journal | EMBO Rep | Pages | e57020 |
| PubMed ID | 37424431 | Mgi Jnum | J:340469 |
| Mgi Id | MGI:7528628 | Doi | 10.15252/embr.202357020 |
| Citation | Dubois-Chevalier J, et al. (2023) An extended transcription factor regulatory network controls hepatocyte identity. EMBO Rep 24(9):e57020 |
| abstractText | 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-ID(CONNECT) TFs also engage in reciprocal transcriptional regulation with TFs of the CoRC. In homeostatic basal conditions, this translates into Hep-ID(CONNECT) TFs being involved in fine tuning CoRC TF expression including their rhythmic expression patterns. Moreover, a role for Hep-ID(CONNECT) TFs in the control of hepatocyte identity is revealed in dedifferentiated hepatocytes where Hep-ID(CONNECT) 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. |
