CoChat
Sign Up
Cited by 46Liver physiology and pathologyEndoplasmic Reticulum Stress and DiseaseDrug-Induced Hepatotoxicity and Protection

Endoplasmic reticulum stress actively suppresses hepatic molecular identity in damaged liver

Open access
Dubois, Vanessa, Gheeraert, Céline, Vankrunkelsven, Wouter, Dubois‐Chevalier, Julie, Dehondt, Hélène, Bobowski‐Gerard, Marie, Vinod, Manjula, Zummo, Francesco Paolo +22 more·2020·Molecular Systems Biology
DOI 10.15252/msb.20199156PMC PMC7224309
Open this paper in CoChat — free accountOpen PDF

Abstract

Liver injury triggers adaptive remodeling of the hepatic transcriptome for repair/regeneration. We demonstrate that this involves particularly profound transcriptomic alterations where acute induction of genes involved in handling of endoplasmic reticulum stress (ERS) is accompanied by partial hepatic dedifferentiation. Importantly, widespread hepatic gene downregulation could not simply be ascribed to cofactor squelching secondary to ERS gene induction, but rather involves a combination of active repressive mechanisms. ERS acts through inhibition of the liver‐identity (LIVER‐ID) transcription factor (TF) network, initiated by rapid LIVER‐ID TF protein loss. In addition, induction of the transcriptional repressor NFIL3 further contributes to LIVER‐ID gene repression. Alteration to the liver TF repertoire translates into compromised activity of regulatory regions characterized by the densest co‐recruitment of LIVER‐ID TFs and decommissioning of BRD4 super‐enhancers driving hepatic identity. While transient repression of the hepatic molecular identity is an intrinsic part of liver repair, sustained disequilibrium between the ERS and LIVER‐ID transcriptional programs is linked to liver dysfunction as shown using mouse models of acute liver injury and livers from deceased human septic patients.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.15252/msb.20199156

Cites

9 of 9 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Breakdown in liver functions in advanced stages of liver injuries and in cancer results from hepatocyte loss of identity stemming from compromised expression of the hepatic core transcriptional regulatory circuitry transcription factors.

    “breakdown in liver functions in advanced stages of liver injuries and in cancer results from hepatocyte loss of identity stemming from compromised expression of the hepatic CoRC TFs (Dubois et al, 2020a; Berasain et al, 2022).”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Dubois et al, 2020a

    The Abstract and Discussion link sustained liver dysfunction after injury to loss of hepatic molecular identity and reduced LIVER-ID transcription-factor activity. The Results examine acute injury in mice and dysfunctional livers from patients with sepsis; they do not establish the same explanation for cancer or advanced stages of liver injury. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Many Hep-IDCONNECT TFs, including NR1H3 and THRB, do not display typically used features to define hepatocyte identity TFs such as hepatocyte-specific expression and association with super-enhancers.

    “Many Hep‐IDCONNECT TFs, including NR1H3 and THRB, do not display typically used features to define hepatocyte identity TFs such as hepatocyte‐specific expression and association with super‐enhancers (Hnisz et al, 2013; Dubois et al, 2020a; Table EV3).”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Dubois et al, 2020a

    The Results section on the LIVER-ID TF network describes high, liver-specific expression as one way to define identity TFs, while the super-enhancer Results section links super-enhancers to liver-identity genes. Neither section establishes the claim’s central point: that many Hep-IDCONNECT TFs, specifically NR1H3 and THRB, lack those features. Searches for Hep-IDCONNECT and both TF names found no passage addressing that comparison; page numbers were unavailable in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Mining transcriptomic data from livers of mice with hepatocyte-specific deletion of individual Hep-IDCONNECT transcription factor-encoding genes indicated a preferential dysregulation of downstream hepatocyte identity effector genes.

    “Mining transcriptomic data obtained from the livers of mice with hepatocyte‐specific deletion of individual Hep‐IDCONNECT TF‐encoding genes (hep−/− mice) indicated that this is functionally underlain by a preferential dysregulation of downstream hepatocyte identity effector genes, that is, non‐TF genes with liver‐specific broad H3K4me3 domains defined in Dubois et al (2020a) (Fig 2H).”

    From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Dubois et al, 2020a

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 90

  1. Abu Rmilah A, Zhou W, Nelson E, Lin L, Amiot B, Nyberg SL (2019) Understanding the marvels behind liver regeneration. Wiley Interdiscip Rev Dev Biol 8: e340 30924280 PMC6457252
  2. Afgan E, Baker D, Batut B, van den Beek M, Bouvier D, Cech M, Chilton J, Clements D, Coraor N, Gruning BA et al (2018) The galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update. Nucleic Acids Res 46: W537– W544 29790989 PMC6030816
  3. Almanza A, Carlesso A, Chintha C, Creedican S, Doultsinos D, Leuzzi B, Luis A, McCarthy N, Montibeller L, More S et al (2019) Endoplasmic reticulum stress signalling ‐ from basic mechanisms to clinical applications. FEBS J 286: 241– 278 30027602 PMC7379631
  4. Anders S, Huber W (2010) Differential expression analysis for sequence count data. Genome Biol 11: R106 20979621 PMC3218662
  5. Arensdorf AM, Dezwaan McCabe D, Kaufman RJ, Rutkowski DT (2013) Temporal clustering of gene expression links the metabolic transcription factor HNF4alpha to the ER stress‐dependent gene regulatory network. Front Genet 4: 188 24069029 PMC3781334
  6. Argemi J, Kress TR, Chang HC, Ferrero R, Bertolo C, Moreno H, Gonzalez‐Aparicio M, Uriarte I, Guembe L, Segura V et al (2017) X‐box binding protein 1 regulates unfolded protein, acute‐phase, and DNA damage responses during regeneration of mouse liver. Gastroenterology 152: 1203– 1216 e15 28082079
  7. Bantubungi K, Hannou S‐A, Caron‐Houde S, Vallez E, Baron M, Lucas A, Bouchaert E, Paumelle R, Tailleux A, Staels B (2014) Cdkn2a/p16Ink4a regulates fasting‐induced hepatic gluconeogenesis through the PKA‐CREB‐PGC1α pathway. Diabetes 63: 3199– 3209 24789920
  8. Benegiamo G, Mure LS, Erikson G, Le HD, Moriggi E, Brown SA, Panda S (2018) The RNA‐binding protein NONO coordinates hepatic adaptation to feeding. Cell Metab 27: 404– 418 e7 29358041 PMC6996513
  9. Bhate A, Parker DJ, Bebee TW, Ahn J, Arif W, Rashan EH, Chorghade S, Chau A, Lee JH, Anakk S et al (2015) ESRP2 controls an adult splicing programme in hepatocytes to support postnatal liver maturation. Nat Commun 6: 8768 26531099 PMC4635967
  10. Brennecke P, Anders S, Kim JK, Kolodziejczyk AA, Zhang X, Proserpio V, Baying B, Benes V, Teichmann SA, Marioni JC et al (2013) Accounting for technical noise in single‐cell RNA‐seq experiments. Nat Methods 10: 1093– 1095 24056876
  11. Brewer JW (2014) Regulatory crosstalk within the mammalian unfolded protein response. Cell Mol Life Sci 71: 1067– 1079 24135849 PMC11113126
  12. Brown JD, Lin CY, Duan Q, Griffin G, Federation A, Paranal RM, Bair S, Newton G, Lichtman A, Kung A et al (2014) NF‐kappaB directs dynamic super enhancer formation in inflammation and atherogenesis. Mol Cell 56: 219– 231 25263595 PMC4224636
  13. Chellappa K, Jankova L, Schnabl JM, Pan S, Brelivet Y, Fung CL, Chan C, Dent OF, Clarke SJ, Robertson GR et al (2012) Src tyrosine kinase phosphorylation of nuclear receptor HNF4alpha correlates with isoform‐specific loss of HNF4alpha in human colon cancer. Proc Natl Acad Sci USA 109: 2302– 2307 22308320 PMC3289305
  14. Chen J, Bardes EE, Aronow BJ, Jegga AG (2009) ToppGene suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res 37: W305– W311 19465376 PMC2703978
  15. Chikka MR, McCabe DD, Tyra HM, Rutkowski DT (2013) C/EBP homologous protein (CHOP) contributes to suppression of metabolic genes during endoplasmic reticulum stress in the liver. J Biol Chem 288: 4405– 4415 23281479 PMC3567690
  16. D'Alessio Ana C, Fan Zi P, Wert Katherine J, Baranov P, Cohen Malkiel A, Saini Janmeet S, Cohick E, Charniga C, Dadon D, Hannett Nancy M et al (2015) A systematic approach to identify candidate transcription factors that control cell identity. Stem Cell Rep 5: 763– 775 PMC4649293 26603904
  17. Dallas PB, Gottardo NG, Firth MJ, Beesley AH, Hoffmann K, Terry PA, Freitas JR, Boag JM, Cummings AJ, Kees UR (2005) Gene expression levels assessed by oligonucleotide microarray analysis and quantitative real‐time RT‐PCR – how well do they correlate? BMC Genom 6: 59 PMC1142514 15854232
  18. Derde S, Thiessen S, Goossens C, Dufour T, Van den Berghe G, Langouche L (2017) Use of a central venous line for fluids, drugs and nutrient administration in a mouse model of critical illness. J Vis Exp e55553 PMC5565154 28518095
  19. Di Micco R, Fontanals‐Cirera B, Low V, Ntziachristos P, Yuen SK, Lovell CD, Dolgalev I, Yonekubo Y, Zhang G, Rusinova E et al (2014) Control of embryonic stem cell identity by BRD4‐dependent transcriptional elongation of super‐enhancer‐associated pluripotency genes. Cell Rep 9: 234– 247 25263550 PMC4317728
  20. Dreszer TR, Karolchik D, Zweig AS, Hinrichs AS, Raney BJ, Kuhn RM, Meyer LR, Wong M, Sloan CA, Rosenbloom KR et al (2012) The UCSC genome browser database: extensions and updates 2011. Nucleic Acids Res 40: D918– D923 22086951 PMC3245018
  21. Dubois‐Chevalier J, Dubois V, Dehondt H, Mazrooei P, Mazuy C, Sérandour AA, Gheeraert C, Guillaume P, Baugé E, Derudas B et al (2017) The logic of transcriptional regulator recruitment architecture at cis‐regulatory modules controlling liver functions. Genome Res 27: 985– 996 28400425 PMC5453331
  22. Edgar R, Domrachev M, Lash AE (2002) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30: 207– 210 11752295 PMC99122
  23. Encode_Project_Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57– 74 22955616 PMC3439153
  24. Ernst J, Nau GJ, Bar‐Joseph Z (2005) Clustering short time series gene expression data. Bioinformatics 21(Suppl 1): i159– i168 15961453
  25. Felix MA, Barkoulas M (2015) Pervasive robustness in biological systems. Nat Rev Genet 16: 483– 496 26184598
  26. Fink EE, Moparthy S, Bagati A, Bianchi‐Smiraglia A, Lipchick BC, Wolff DW, Roll MV, Wang J, Liu S, Bakin AV et al (2018) XBP1‐KLF9 axis acts as a molecular rheostat to control the transition from adaptive to cytotoxic unfolded protein response. Cell Rep 25: 212– 223 e4 30282030 PMC6251307
  27. Frankish A, Diekhans M, Ferreira AM, Johnson R, Jungreis I, Loveland J, Mudge JM, Sisu C, Wright J, Armstrong J et al (2019) GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res 47: D766– D773 30357393 PMC6323946
  28. Freese NH, Norris DC, Loraine AE (2016) Integrated genome browser: visual analytics platform for genomics. Bioinformatics 32: 2089– 2095 27153568 PMC4937187
  29. Gachon F, Olela FF, Schaad O, Descombes P, Schibler U (2006) The circadian PAR‐domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification. Cell Metab 4: 25– 36 16814730
  30. Gjuvsland AB, Plahte E, Omholt SW (2007) Threshold‐dominated regulation hides genetic variation in gene expression networks. BMC Syst Biol 1: 57 18062810 PMC2238762
  31. Harding HP, Zhang Y, Bertolotti A, Zeng H, Ron D (2000) Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol Cell 5: 897– 904 10882126
  32. Hetz C (2012) The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 13: 89– 102 22251901
  33. Huck I, Gunewardena S, Espanol‐Suner R, Willenbring H, Apte U (2019) Hepatocyte nuclear factor 4 alpha activation is essential for termination of liver regeneration in mice. Hepatology 70: 666– 681 30520062 PMC6551324
  34. van der Kallen LR, Eggers R, Ehlert EM, Verhaagen J, Smit AB, van Kesteren RE (2015) Genetic deletion of the transcriptional repressor NFIL3 enhances axon growth in vitro but not axonal repair in vivo. PLoS ONE 10: e0127163 25993115 PMC4438979
  35. Kalvisa A, Siersbaek MS, Praestholm SM, Christensen LJL, Nielsen R, Stohr O, Vettorazzi S, Tuckermann J, White M, Mandrup S et al (2018) Insulin signaling and reduced glucocorticoid receptor activity attenuate postprandial gene expression in liver. PLoS Biol 16: e2006249 30532187 PMC6301715
  36. Kim YH, Marhon SA, Zhang Y, Steger DJ, Won K‐J, Lazar MA (2018) Rev‐erbα dynamically modulates chromatin looping to control circadian gene transcription. Science 359: 1274– 1277 29439026 PMC5995144
  37. Kyrmizi I, Hatzis P, Katrakili N, Tronche F, Gonzalez FJ, Talianidis I (2006) Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev 20: 2293– 2305 16912278 PMC1553211
  38. Lai L, Hennessey J, Bares V, Son EW, Ban Y, Wang W, Qi J, Jiang G, Liberzon A, Xijin Ge S (2016) GSKB: a gene set database for pathway analysis in mouse. bioRxiv, 10.1101/082511 [PREPRINT] · DOI
  39. Langmead B, Salzberg SL (2012) Fast gapped‐read alignment with Bowtie 2. Nat Methods 9: 357– 359 22388286 PMC3322381
  40. Langmead B, Trapnell C, Pop M, Salzberg SL (2009) Ultrafast and memory‐efficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25 19261174 PMC2690996
  41. Lau HH, Ng NHJ, Loo LSW, Jasmen JB, Teo AKK (2018) The molecular functions of hepatocyte nuclear factors ‐ In and beyond the liver. J Hepatol 68: 1033– 1048 29175243
  42. Lawrence M, Huber W, Pages H, Aboyoun P, Carlson M, Gentleman R, Morgan MT, Carey VJ (2013) Software for computing and annotating genomic ranges. PLoS Comput Biol 9: e1003118 23950696 PMC3738458
  43. Lee JE, Park YK, Park S, Jang Y, Waring N, Dey A, Ozato K, Lai B, Peng W, Ge K (2017) Brd4 binds to active enhancers to control cell identity gene induction in adipogenesis and myogenesis. Nat Commun 8: 2217 29263365 PMC5738375
  44. Levo M, Avnit‐Sagi T, Lotan‐Pompan M, Kalma Y, Weinberger A, Yakhini Z, Segal E (2017) Systematic investigation of transcription factor activity in the context of chromatin using massively parallel binding and expression assays. Mol Cell 65: 604– 617 e6 28212748
  45. Li T, Huang J, Jiang Y, Zeng Y, He F, Zhang MQ, Han Z, Zhang X (2009) Multi‐stage analysis of gene expression and transcription regulation in C57/B6 mouse liver development. Genomics 93: 235– 242 19015022 PMC2995988
  46. Liu CY, Chen KF, Chen PJ (2015a) Treatment of liver cancer. Cold Spring Harb Perspect Med 5: a021535 26187874 PMC4561392
  47. Liu Y, Shao M, Wu Y, Yan C, Jiang S, Liu J, Dai J, Yang L, Li J, Jia W et al (2015b) Role for the endoplasmic reticulum stress sensor IRE1alpha in liver regenerative responses. J Hepatol 62: 590– 598 25457211
  48. Lun AT, Smyth GK (2014) De novo detection of differentially bound regions for ChIP‐seq data using peaks and windows: controlling error rates correctly. Nucleic Acids Res 42: e95 24852250 PMC4066778
  49. Lun AT, Smyth GK (2016) csaw: a bioconductor package for differential binding analysis of ChIP‐seq data using sliding windows. Nucleic Acids Res 44: e45 26578583 PMC4797262
  50. von Meyenn F, Porstmann T, Gasser E, Selevsek N, Schmidt A, Aebersold R, Stoffel M (2013) Glucagon‐induced acetylation of Foxa2 regulates hepatic lipid metabolism. Cell Metab 17: 436– 447 23416070
  51. Mitsui S, Yamaguchi S, Matsuo T, Ishida Y, Okamura H (2001) Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory mechanism. Genes Dev 15: 995– 1006 11316793 PMC312673
  52. Mudunuri U, Che A, Yi M, Stephens RM (2009) bioDBnet: the biological database network. Bioinformatics 25: 555– 556 19129209 PMC2642638
  53. Nesseler N, Launey Y, Aninat C, Morel F, Mallédant Y, Seguin P (2012) Clinical review: the liver in sepsis. Crit Care 16: 235 23134597 PMC3682239
  54. O'Connor T, Boden M, Bailey TL (2017) CisMapper: predicting regulatory interactions from transcription factor ChIP‐seq data. Nucleic Acids Res 45: e19 28204599 PMC5389714
  55. Ohta Y, Taguchi A, Matsumura T, Nakabayashi H, Akiyama M, Yamamoto K, Fujimoto R, Suetomi R, Yanai A, Shinoda K et al (2017) Clock gene dysregulation induced by chronic ER stress disrupts beta‐cell function. EBioMedicine 18: 146– 156 28389215 PMC5405175
  56. Paumelle R, Haas J, Hennuyer N, Bauge E, Deleye Y, Mesotten D, Langouche L, Vanhoutte J, Cudejko C, Wouters K et al (2019) Hepatic PPARa is critical in the metabolic adaptation to sepsis. J Hepatol 70: 963– 973 30677458 PMC6774768
  57. Peng L, Piekos SC, Guo GL, Zhong X‐b (2017) Role of farnesoid X receptor in the determination of liver transcriptome during postnatal maturation in mice. Nuclear Recep Res 4: 101308 PMC5962295 29795774
  58. Ploton M, Mazuy C, Gheeraert C, Dubois V, Berthier A, Dubois‐Chevalier J, Marechal X, Bantubungi K, Diemer H, Cianferani S et al (2018) The nuclear bile acid receptor FXR is a PKA‐ and FOXA2‐sensitive activator of fasting hepatic gluconeogenesis. J Hepatol 69: 1099– 1109 29981427
  59. Reimold AM, Etkin A, Clauss I, Perkins A, Friend DS, Zhang J, Horton HF, Scott A, Orkin SH, Byrne MC et al (2000) An essential role in liver development for transcription factor XBP‐1. Genes Dev 14: 152– 157 10652269 PMC316338
  60. Rib L, Villeneuve D, Minocha S, Praz V, Hernandez N, Guex N, Herr W, Cycli XC (2018) Cycles of gene expression and genome response during mammalian tissue regeneration. Epigenetics Chromatin 11: 52 30208973 PMC6134763
  61. Roe JS, Mercan F, Rivera K, Pappin DJ, Vakoc CR (2015) BET bromodomain inhibition suppresses the function of hematopoietic transcription factors in acute myeloid leukemia. Mol Cell 58: 1028– 1039 25982114 PMC4475489
  62. Rutkowski DT (2019) Liver function and dysfunction ‐ a unique window into the physiological reach of ER stress and the unfolded protein response. FEBS J 286: 356– 378 29360258 PMC6056347
  63. Santiago‐Algarra D, Dao LTM, Pradel L, Espana A, Spicuglia S (2017) Recent advances in high‐throughput approaches to dissect enhancer function. 1000Res 66: 939 PMC5482341 28690838
  64. Schmidt SF, Larsen BD, Loft A, Nielsen R, Madsen JG, Mandrup S (2015) Acute TNF‐induced repression of cell identity genes is mediated by NFkappaB‐directed redistribution of cofactors from super‐enhancers. Genome Res 25: 1281– 1294 26113076 PMC4561488
  65. Schmidt SF, Larsen BD, Loft A, Mandrup S (2016) Cofactor squelching: artifact or fact? BioEssays 38: 618– 626 27273739
  66. Sheffield NC, Bock C (2016) LOLA: enrichment analysis for genomic region sets and regulatory elements in R and Bioconductor. Bioinformatics 32: 587– 589 26508757 PMC4743627
  67. Silveira MAD, Bilodeau S (2018) Defining the transcriptional ecosystem. Mol Cell 72: 920– 924 30576654
  68. Spinelli L, Carpentier S, Montanana Sanchis F, Dalod M, Vu Manh TP (2015) BubbleGUM: automatic extraction of phenotype molecular signatures and comprehensive visualization of multiple gene set enrichment analyses. BMC Genom 16: 814 PMC4617899 26481321
  69. Suaud L, Formstecher P, Laine B (1999) The activity of the activation function 2 of the human hepatocyte nuclear factor 4 (HNF‐4alpha) is differently modulated by F domains from various origins. Biochem J 340(Pt 1): 161– 169 10229671 PMC1220234
  70. Takasu O, Gaut JP, Watanabe E, To K, Fagley RE, Sato B, Jarman S, Efimov IR, Janks DL, Srivastava A et al (2013) Mechanisms of cardiac and renal dysfunction in patients dying of sepsis. Am J Respir Crit Care Med 187: 509– 517 23348975 PMC3733408
  71. Thiessen SE, Derde S, Derese I, Dufour T, Vega CA, Langouche L, Goossens C, Peersman N, Vermeersch P, Vander Perre S et al (2017) Role of glucagon in catabolism and muscle wasting of critical illness and modulation by nutrition. Am J Respir Crit Care Med 196: 1131– 1143 28475354
  72. Tsai YL, Ha DP, Zhao H, Carlos AJ, Wei S, Pun TK, Wu K, Zandi E, Kelly K, Lee AS (2018) Endoplasmic reticulum stress activates SRC, relocating chaperones to the cell surface where GRP78/CD109 blocks TGF‐beta signaling. Proc Natl Acad Sci USA 115: E4245– E4254 29654145 PMC5939063
  73. Vandel J, Gheeraert C, Eeckhoute J, Staels B, Lefebvre P, Dubois‐Chevalier J (2018) GIANT: Galaxy‐based Interactive tools for ANalaysis of Transcriptomic data PMC7670435 33199699
  74. Vihervaara A, Duarte FM, Lis JT (2018) Molecular mechanisms driving transcriptional stress responses. Nat Rev Genet 19: 385– 397 29556092 PMC6036639
  75. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG (1996) The SOFA (Sepsis‐related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis‐Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 22: 707– 710 8844239
  76. Wang W, Yao LJ, Shen W, Ding K, Shi PM, Chen F, He J, Ding J, Zhang X, Xie WF (2017) FOXA2 alleviates CCl4‐induced liver fibrosis by protecting hepatocytes in mice. Sci Rep 7: 15532 29138513 PMC5686201
  77. Wang J, Hu B, Zhao Z, Zhang H, Zhang H, Zhao Z, Ma X, Shen B, Sun B, Huang X et al (2020) Intracellular XBP1‐IL‐24 axis dismantles cytotoxic unfolded protein response in the liver. Cell Death Dis 11: 17 31907348 PMC6944701
  78. Wei J, Chen L, Li F, Yuan Y, Wang Y, Xia W, Zhang Y, Xu Y, Yang Z, Gao B et al (2018) HRD1‐ERAD controls production of the hepatokine FGF21 through CREBH polyubiquitination. EMBO J 37: e98942 30389664 PMC6236336
  79. White P, Brestelli JE, Kaestner KH, Greenbaum LE (2005) Identification of transcriptional networks during liver regeneration. J Biol Chem 280: 3715– 3722 15546871
  80. Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA (2013) Master transcription factors and mediator establish super‐enhancers at key cell identity genes. Cell 153: 307– 319 23582322 PMC3653129
  81. Woznica EA, Inglot M, Woznica RK, Lysenko L (2018) Liver dysfunction in sepsis. Adv Clin Exp Med 27: 547– 551 29558045
  82. Wu C, Jin X, Tsueng G, Afrasiabi C, Su AI (2016) BioGPS: building your own mash‐up of gene annotations and expression profiles. Nucleic Acids Res 44: D313– D316 26578587 PMC4702805
  83. Wu SY, Lee AY, Hou SY, Kemper JK, Erdjument‐Bromage H, Tempst P, Chiang CM (2006) Brd4 links chromatin targeting to HPV transcriptional silencing. Genes Dev 20: 2383– 2396 16921027 PMC1560413
  84. Yang L, Wang WH, Qiu WL, Guo Z, Bi E, Xu CR (2017) A single‐cell transcriptomic analysis reveals precise pathways and regulatory mechanisms underlying hepatoblast differentiation. Hepatology 66: 1387– 1401 28681484 PMC5650503
  85. Yevshin I, Sharipov R, Valeev T, Kel A, Kolpakov F (2017) GTRD: a database of transcription factor binding sites identified by ChIP‐seq experiments. Nucleic Acids Res 45: D61– D67 27924024 PMC5210645
  86. Yue F, Cheng Y, Breschi A, Vierstra J, Wu W, Ryba T, Sandstrom R, Ma Z, Davis C, Pope BD et al (2014) A comparative encyclopedia of DNA elements in the mouse genome. Nature 515: 355– 364 25409824 PMC4266106
  87. Zengerle M, Chan KH, Ciulli A (2015) Selective small molecule induced degradation of the BET bromodomain protein BRD4. ACS Chem Biol 10: 1770– 1777 26035625 PMC4548256
  88. Zhang HM, Liu T, Liu CJ, Song S, Zhang X, Liu W, Jia H, Xue Y, Guo AY (2015) AnimalTFDB 2.0: a resource for expression, prediction and functional study of animal transcription factors. Nucleic Acids Res 43: D76– D81 25262351 PMC4384004
  89. Zhou Y, Lee J, Reno CM, Sun C, Park SW, Chung J, Lee J, Fisher SJ, White MF, Biddinger SB et al (2011) Regulation of glucose homeostasis through a XBP‐1‐FoxO1 interaction. Nat Med 17: 356– 365 21317886 PMC3897616
  90. Zhou Q, Liu M, Xia X, Gong T, Feng J, Liu W, Liu Y, Zhen B, Wang Y, Ding C et al (2017) A mouse tissue transcription factor atlas. Nat Commun 8: 15089 28429721 PMC5413951

Cited by

Sorted by citations

Authors
Dubois, V., Gheeraert, C., Vankrunkelsven, W., Dubois‐Chevalier, J., Dehondt, H., Bobowski‐Gerard, M., Vinod, M., Zummo, F. P., Güiza, F., Ploton, M., Dorchies, E., Pineau, L., Boulinguiez, A., Vallez, E., Woitrain, E., Baugé, E., Lalloyer, F., Duhem, C., Rabhi, N., van Kesteren, R. E., Chiang, C., Lancel, S., Duez, H., Annicotte, J., Paumelle, R., Vanhorebeek, I., Van den Berghe, G., Staels, B., Lefebvre, P., & Eeckhoute, J.
Affiliations
  • Inserm (FR)
  • KU Leuven (BE)
  • Centre National de la Recherche Scientifique (FR)
  • Harold C. Simmons Comprehensive Cancer Center (US)
Corresponding author
Eeckhoute, Jérôme
ORCID
Venue
Molecular Systems Biology
Publisher
Springer Science and Business Media LLC
Published
2020-05-01
Volume
16
Issue
5
Pages
e9156-e9156
ISSN
1744-4292 (ISSN-L)
DOI
10.15252/msb.20199156
PMC
PMC7224309
OpenAlex
W3024451001
Cited by
46
References
9
Citations by year
2026: 4 · 2025: 3 · 2024: 15 · 2023: 8 · 2022: 5 · 2021: 8 · 2020: 3
FWCI
3.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Systems Biology (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • VU Research Portal (publishedVersion, other-oa)
  • HAL (submittedVersion, other-oa)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
  • Lirias (KU Leuven) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • Fondation pour la Recherche Médicale (DEQ20150331724)
  • Agence Nationale de la Recherche (ANR‐10‐LABX‐46)
  • H2020 European Research Council (694717)
  • National Institutes of Health (1RO1CA251698‐01)
  • Cancer Prevention and Research Institute of Texas (RP180349, RP190077)
  • Welch Foundation (I‐1805)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
endoplasmic reticulum stress, liver injury, liver regeneration, NFIL3, transcriptional repression, super-enhancers, BRD4, liver transcriptome, sepsis, acute liver injury
MeSH terms
Chromatin Immunoprecipitation Sequencing, Bromodomain Containing Proteins, Animals, Cell Line, Cells, Cultured, Gene Expression Regulation, Humans, Liver Diseases, Male, Mice, Inbred C57BL, Nuclear Proteins, Transcription Factors, Down-Regulation, Up-Regulation, Mice, Knockout, Cell Cycle Proteins, Thapsigargin, Gene Expression Profiling, Hepatocytes, Basic-Leucine Zipper Transcription Factors, Mice, Gene Regulatory Networks, Chemical and Drug Induced Liver Injury, Transcriptome, Endoplasmic Reticulum Stress

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review