CoChat
Sign Up
Cited by 39Genomics and Chromatin DynamicsCircadian rhythm and melatoninPlant Molecular Biology Research

The global and promoter-centric 3D genome organization temporally resolved during a circadian cycle

Open access
Furlan-Magaril, Mayra, Ando-Kuri, Masami, Arzate-Mejía, Rodrigo G., Morf, Jörg, Cairns, Jonathan, Román-Figueroa, Abraham, Tenorio-Hernández, Luis, Poot-Hernández, A. César +5 more·2021·Genome Biology
DOI 10.1186/s13059-021-02374-3PMC PMC8185950

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Circadian gene expression is essential for organisms to adjust their physiology and anticipate daily changes in the environment. The molecular mechanisms controlling circadian gene transcription are still under investigation. In particular, how chromatin conformation at different genomic scales and regulatory elements impact rhythmic gene expression has been poorly characterized. Results: Here we measure changes in the spatial chromatin conformation in mouse liver using genome-wide and promoter-capture Hi-C alongside daily oscillations in gene transcription. We find topologically associating domains harboring circadian genes that switch assignments between the transcriptionally active and inactive compartment at different hours of the day, while their boundaries stably maintain their structure over time. To study chromatin contacts of promoters at high resolution over time, we apply promoter capture Hi-C. We find circadian gene promoters displayed a maximal number of chromatin contacts at the time of their peak transcriptional output. Furthermore, circadian genes, as well as contacted and transcribed regulatory elements, reach maximal expression at the same timepoints. Anchor sites of circadian gene promoter loops are enriched in DNA binding sites for liver nuclear receptors and other transcription factors, some exclusively present in either rhythmic or stable contacts. Finally, by comparing the interaction profiles between core clock and output circadian genes, we show that core clock interactomes are more dynamic compared to output circadian genes. Conclusion: Our results identify chromatin conformation dynamics at different scales that parallel oscillatory gene expression and characterize the repertoire of regulatory elements that control circadian gene transcription through rhythmic or stable chromatin configurations.

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 · 10.1186/s13059-021-02374-3

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?

  • Around one-sixth of the genome undergoes compartment changes during the 24 h circadian cycle in mouse adult liver.

    “around 1/6th of the genome undergoes compartment changes during the 24 h circadian cycle in mouse adult liver [458].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [458]

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: 57

  1. [1]Zhang R Lahens NF Ballance HI Hughes ME Hogenesch JB A circadian gene expression atlas in mammals: implications for biology and medicine Proc Natl Acad Sci U S A. 2014 111 45 16219 16224 10.1073/pnas.1408886111 25349387 PMC4234565 · DOI · Paper page
  2. [2]Takahashi JS Transcriptional architecture of the mammalian circadian clock Nat Rev Genet 2017 18 3 164 179 10.1038/nrg.2016.150 27990019 PMC5501165 · DOI
  3. [3]Aguilar-Arnal L Hakim O Patel VR Baldi P Hager GL Sassone-Corsi P Cycles in spatial and temporal chromosomal organization driven by the circadian clock Nat Struct Mol Biol 2013 20 10 1206 1213 10.1038/nsmb.2667 24056944 PMC3885543 · DOI
  4. [4]Mermet J Yeung J Hurni C Mauvoisin D Gustafson K Jouffe C Nicolas D Emmenegger Y Gobet C Franken P Gachon F Naef F Clock-dependent chromatin topology modulates circadian transcription and behavior Genes Dev 2018 32 5–6 347 358 10.1101/gad.312397.118 29572261 PMC5900709 · DOI
  5. [5]Yeung J Mermet J Jouffe C Marquis J Charpagne A Gachon F Naef F Transcription factor activity rhythms and tissue-specific chromatin interactions explain circadian gene expression across organs Genome Res 2018 28 2 182 191 10.1101/gr.222430.117 29254942 PMC5793782 · DOI
  6. [6]Yeung J Naef F Rhythms of the genome: circadian dynamics from chromatin topology, tissue-specific gene expression, to behavior Trends Genet 2018 34 12 915 926 10.1016/j.tig.2018.09.005 30309754 · DOI
  7. [7]Beytebiere JR Trott AJ Greenwell B Osborne CA Vitet H Spence J Tissue-specific BMAL1 cistromes reveal that enhancer-enhancer interactions regulate rhythmic transcription Genes Dev 2019 33 5-6 294 309 10.1101/gad.322198.118 30804225 PMC6411008 · DOI
  8. [8]Xu Y, Guo W, Li P, Zhang Y, Zhao M, Fan Z, et al. Long-range chromosome interactions mediated by cohesin shape circadian gene expression. PLoS Genet. 2016;12(5):e1005992. 10.1371/journal.pgen.1005992. PMC4852938 27135601 · DOI
  9. [9]Kim YH Marhon SA Zhang Y Steger DJ Won K-J Lazar MA Rev-erbα dynamically modulates chromatin looping to control circadian gene transcription Science. 2018 359 6381 1274 1277 10.1126/science.aao6891 29439026 PMC5995144 · DOI
  10. [10]Lieberman-Aiden E van Berkum NL Williams L Imakaev M Ragoczy T Telling A Amit I Lajoie BR Sabo PJ Dorschner MO Sandstrom R Bernstein B Bender MA Groudine M Gnirke A Stamatoyannopoulos J Mirny LA Lander ES Dekker J Comprehensive mapping of long-range interactions reveals folding principles of the human genome Science. 2009 326 5950 289 293 10.1126/science.1181369 19815776 PMC2858594 · DOI · Paper page
  11. [14]Sun Z Feng D Fang B Mullican SE You SH Lim HW Everett LJ Nabel CS Li Y Selvakumaran V Won KJ Lazar MA Deacetylase-Independent function of HDAC3 in transcription and metabolism requires nuclear receptor corepressor Mol Cell. 2013 52 6 769 782 10.1016/j.molcel.2013.10.022 24268577 PMC3877208 · DOI
  12. [15]Crane E Bian Q McCord RP Lajoie BR Wheeler BS Ralston EJ Uzawa S Dekker J Meyer BJ Condensin-driven remodelling of X chromosome topology during dosage compensation Nature. 2015 523 7559 240 244 10.1038/nature14450 26030525 PMC4498965 · DOI
  13. [17]Merkenschlager M Nora EP CTCF and cohesin in genome folding and transcriptional gene regulation Annu Rev Genomics Hum Genet 2016 17 1 17 43 10.1146/annurev-genom-083115-022339 27089971 · DOI
  14. [22]Schoenfelder S Furlan-Magaril M Mifsud B Tavares-Cadete F Sugar R Javierre BM Nagano T Katsman Y Sakthidevi M Wingett SW Dimitrova E Dimond A Edelman LB Elderkin S Tabbada K Darbo E Andrews S Herman B Higgs A LeProust E Osborne CS Mitchell JA Luscombe NM Fraser P The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements Genome Res 2015 25 4 582 597 10.1101/gr.185272.114 25752748 PMC4381529 · DOI · Paper page
  15. [23]Schoenfelder S Sugar R Dimond A Javierre B Armstrong H Mifsud B Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome Nat Genet 2015 47 10 1179 1186 10.1038/ng.3393 26323060 PMC4847639 · DOI · Paper page
  16. [25]Raudvere U Kolberg L Kuzmin I Arak T Adler P Peterson H Vilo J g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update) Nucleic Acids Res 2019 47 191 198 10.1093/nar/gkz369 PMC6602461 31066453 · DOI · Paper page
  17. [26]Spengler U Pape GR Hoffmann RM Johnson JP Eisenburg J Paumgartner G Riethmüller G Differential expression of MHC class II subregion products on bile duct epithelial cells and hepatocytes in patients with primary biliary cirrhosis Hepatology 1988 8 3 459 462 10.1002/hep.1840080304 3371866 · DOI
  18. [27]Fang B Everett LJ Jager J Briggs E Armour SM Feng D Roy A Gerhart-Hines Z Sun Z Lazar MA Circadian enhancers coordinate multiple phases of rhythmic gene transcription in vivo Cell. 2014 159 5 1140 1152 10.1016/j.cell.2014.10.022 25416951 PMC4243056 · DOI
  19. [28]Yue F Cheng Y Breschi A Vierstra J Wu W Ryba T A comparative encyclopedia of DNA elements in the mouse genome Nature. 2014 515 7527 355 364 10.1038/nature13992 25409824 PMC4266106 · DOI · Paper page
  20. [29]Sobel JA Krier I Andersin T Raghav S Canella D Gilardi F Kalantzi AS Rey G Weger B Gachon F Dal Peraro M Hernandez N Schibler U Deplancke B Naef F CycliX consortium Transcriptional regulatory logic of the diurnal cycle in the mouse liver PLoS Biology. 2017 15 4 e2001069 10.1371/journal.pbio.2001069 28414715 PMC5393560 · DOI
  21. [30]Bailey TL Johnson J Grant CE Noble WS The MEME Suite Nucleic Acids Res 2015 43 39 49 10.1093/nar/gkv416 PMC4489269 25953851 · DOI
  22. [31]Chen F Ma L Dawson PA Sinal CJ Sehayek E Gonzalez FJ Breslow J Ananthanarayanan M Shneider BL Liver receptor homologue-1 mediates species- and cell line-specific bile acid-dependent negative feedback regulation of the apical sodium-dependent bile acid transporter J Biol Chem 2003 278 22 19909 19916 10.1074/jbc.M207903200 12456679 · DOI
  23. [32]Chong HK Biesinger J Seo Y-K Xie X Osborne TF Genome-wide analysis of hepatic LRH-1 reveals a promoter binding preference and suggests a role in regulating genes of lipid metabolism in concert with FXR BMC Genomics 2012 1 13 51 10.1186/1471-2164-13-51 PMC3295688 22296850 · DOI
  24. [33]Matsukuma KE Wang L Bennett MK Osborne TF A key role for orphan nuclear receptor liver receptor homologue-1 in activation of fatty acid synthase promoter by liver X receptor J Biol Chem 2007 282 28 20164 20171 10.1074/jbc.M702895200 17522048 · DOI
  25. [34]Wu N Kim KH Zhou Y Lee J Kettner NM Mamrosh JL Small heterodimer partner (NR0B2) coordinates nutrient signaling and the circadian clock in mice Mol Endocrinol 2016 30 9 988 995 10.1210/me.2015-1295 27427832 PMC5004116 · DOI
  26. [35]Schwaderer J San Phan T Glöckner A Delp J Leist M Brunner T Pharmacological LRH-1/Nr5a2 inhibition limits pro-inflammatory cytokine production in macrophages and associated experimental hepatitis Cell Death Dis. 2020 11 2 154 10.1038/s41419-020-2348-9 32111818 PMC7048823 · DOI
  27. [36]Miranda DA Krause WC Cazenave-Gassiot A Suzawa M Escusa H Foo JC Shihadih DS Stahl A Fitch M Nyangau E Hellerstein M Wenk MR Silver DL Ingraham HA LRH-1 regulates hepatic lipid homeostasis and maintains arachidonoyl phospholipid pools critical for phospholipid diversity JCI Insight. 2018 3 5 e96151 10.1172/jci.insight.96151 PMC5922282 29515023 · DOI
  28. [37]Holl D Kuckenberg P Woynecki T Egert A Becker A Huss S Stabenow D Zimmer A Knolle P Tolba R Fischer HP Schorle H Transgenic overexpression of Tcfap2c/AP-2gamma results in liver failure and intestinal dysplasia PLoS One. 2011 6 7 e22034 10.1371/journal.pone.0022034 21779369 PMC3135619 · DOI
  29. [38]Scott CC Vossio S Rougemont J Gruenberg J TFAP2 transcription factors are regulators of lipid droplet biogenesis ELife. 2018 7 e36330 10.7554/eLife.36330 30256193 PMC6170152 · DOI
  30. [39]Balsalobre A Damiola F Schibler U A serum shock induces circadian gene expression in mammalian tissue culture cells Cell. 1998 93 6 929 937 10.1016/S0092-8674(00)81199-X 9635423 · DOI · Paper page
  31. [40]Chen Y Yamaguchi Y Suzuki T Doi M Okamura H Effect of daily light on c-Fos expression in the suprachiasmatic nucleus under jet lag conditions Acta Histochem Cytochem 2018 51 2 73 80 10.1267/ahc.18001 29867280 PMC5976887 · DOI
  32. [41]Guido ME Goguen D De Guido L Robertson HA Rusak B Circadian and photic regulation of immediate-early gene expression in the hamster suprachiasmatic nucleus Neuroscience. 1999 90 2 555 571 10.1016/S0306-4522(98)00467-9 10215159 · DOI
  33. [42]Schwartz WJ Carpino A De La Iglesia HO Baler R Klein DC Nakabeppu Y Differential regulation of fos family genes in the ventrolateral and dorsomedial subdivisions of the rat suprachiasmatic nucleus Neuroscience. 2000 98 3 535 547 10.1016/S0306-4522(00)00140-8 10869847 · DOI
  34. [43]Phanstiel DH Van Bortle K Spacek D Hess GT Saad Shamim M Machol I Static and dynamic DNA loops form AP-1 bound activation hubs during macrophage development Mol Cell. 2017 67 6 1037 1048 10.1016/j.molcel.2017.08.006 28890333 PMC5610110 · DOI · Paper page
  35. [44]Anafi RC Lee Y Sato TK Venkataraman A Ramanathan C Kavakli IH Hughes ME Baggs JE Growe J Liu AC Kim J Hogenesch JB Machine learning helps identify CHRONO as a circadian clock component PLoS Biol 2014 12 4 e1001840 10.1371/journal.pbio.1001840 24737000 PMC3988006 · DOI
  36. [45]Nagano T Lubling Y Várnai C Dudley C Leung W Baran Y Mendelson Cohen N Wingett S Fraser P Tanay A Cell-cycle dynamics of chromosomal organization at single-cell resolution Nature. 2017 547 7661 61 67 10.1038/nature23001 28682332 PMC5567812 · DOI · Paper page
  37. [46]Mermet J Yeung J Naef F Oscillating and stable genome topologies underlie hepatic physiological rhythms during the circadian cycle PLOS Genet 2021 17 2 e1009350 10.1371/journal.pgen.1009350 33524027 PMC7877755 · DOI
  38. [47]Wingett S, Ewels P, Furlan-Magaril M, Nagano T, Schoenfelder S, Fraser P, et al. HiCUP: pipeline for mapping and processing Hi-C data. F1000Research. 2015; 10.12688/f1000research.7334.1. PMC4706059 26835000 · DOI
  39. [48]Durand NC Robinson JT Shamim MS Machol I Mesirov JP Lander ES Aiden EL Juicebox provides a visualization system for Hi-C contact maps with unlimited zoom Cell Syst 2016 3 1 99 101 10.1016/j.cels.2015.07.012 27467250 PMC5596920 · DOI
  40. [49]Durand NC Shamim MS Machol I Rao SSP Huntley MH Lander ES Aiden EL Juicer provides a one-click system for analyzing loop-resolution Hi-C experiments Cell Syst 2016 3 1 95 98 10.1016/j.cels.2016.07.002 27467249 PMC5846465 · DOI
  41. [50]Kruse K Hug CB Hernández-Rodríguez B Vaquerizas JM TADtool: visual parameter identification for TAD-calling algorithms Bioinformatics 2016 32 20 3190 3192 10.1093/bioinformatics/btw368 27318199 PMC5048066 · DOI
  42. [51]Khan A Mathelier A Intervene: a tool for intersection and visualization of multiple gene or genomic region sets BMC Bioinformatics. 2017 18 1 287 10.1186/s12859-017-1708-7 28569135 PMC5452382 · DOI
  43. [52]Feng D Liu T Sun Z Bugge A Mullican SE Alenghat T Liu XS Lazar MA A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism Science 2011 331 6022 1315 1319 10.1126/science.1198125 21393543 PMC3389392 · DOI · Paper page
  44. [53]McCarthy DJ Chen Y Smyth GK Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation Nucleic Acids Res 2012 40 10 4288 4297 10.1093/nar/gks042 22287627 PMC3378882 · DOI · Paper page
  45. [55]Virtanen P Gommers R Oliphant TE Haberland M Reddy T Cournapeau D SciPy 1.0: fundamental algorithms for scientific computing in Python Nature Methods. 2020 17 3 261 272 10.1038/s41592-019-0686-2 32015543 PMC7056644 · DOI · Paper page
  46. [56]Seabold S Perktold J Statsmodels: econometric and statistical modeling with Python. Proc. Of the 9th python in science conf 2010
  47. [57]Langmead B Salzberg SL Fast gapped-read alignment with Bowtie 2 Nature Methods. 2012 9 4 357 359 10.1038/nmeth.1923 22388286 PMC3322381 · DOI · Paper page
  48. [58]Ramírez F Ryan DP Grüning B Bhardwaj V deepTools2: a next generation web server for deep-sequencing data analysis Nucleic Acids Res. 2016 44 W1 W160 W165 10.1093/nar/gkw257 27079975 PMC4987876 · DOI · Paper page
  49. [59]Thorvaldsdóttir H Robinson JT Mesirov JP Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration Brief Bioinformatics. 2013 14 2 178 192 10.1093/bib/bbs017 22517427 PMC3603213 · DOI · Paper page
  50. [60]Zhang Y Liu T Meyer CA Eeckhoute J Johnson DS Bernstein BE Nussbaum C Myers RM Brown M Li W Liu XS Model-based analysis of ChIP-Seq (MACS) Genome Biol 2008 9 9 R137 10.1186/gb-2008-9-9-r137 18798982 PMC2592715 · DOI · Paper page
  51. [61]Ma W Noble WS Bailey TL Motif-based analysis of large nucleotide data sets using MEME-ChIP Nat Protoc. 2014 9 6 1428 1450 10.1038/nprot.2014.083 24853928 PMC4175909 · DOI
  52. [62]Kim D Pertea G Trapnell C Pimentel H Kelley R Salzberg SL TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions Genome Biol 2013 14 4 R36 10.1186/gb-2013-14-4-r36 23618408 PMC4053844 · DOI · Paper page
  53. [63]Li H Handsaker B Wysoker A Fennell T Ruan J Homer N Marth G Abecasis G Durbin R 1000 Genome Project Data Processing Subgroup The Sequence Alignment/Map format and SAMtools Bioinformatics. 2009 25 16 2078 2079 10.1093/bioinformatics/btp352 19505943 PMC2723002 · DOI · Paper page
  54. [64]Pertea M Pertea GM Antonescu CM Chang T-C Mendell JT Salzberg SL StringTie enables improved reconstruction of a transcriptome from RNA-seq reads Nat Biotechnol 2015 33 3 290 295 10.1038/nbt.3122 25690850 PMC4643835 · DOI
  55. [65]Frazee AC Pertea G Jaffe AE Langmead B Salzberg SL Leek JT Ballgown bridges the gap between transcriptome assembly and expression analysis Nat Biotechnol 2015 33 3 243 246 10.1038/nbt.3172 25748911 PMC4792117 · DOI
  56. [66]Huang DW Sherman BT Lempicki RA Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources Nat Protoc 2009 4 1 44 57 10.1038/nprot.2008.211 19131956 · DOI · Paper page
  57. [67]Furlan-Magaril M, Ando-Kuri M, Arzate-Mejía RG, Morf J, Cairns J, Roman-Figueroa A, et al. The global and promoter-centric 3D genome organization temporally resolved during a circadian cycle. GSE155161. Gene Expression Omnibus. 2020. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE155161. PMC8185950 34099014

Cited by

Sorted by citations

Authors
Furlan-Magaril, M., Ando-Kuri, M., Arzate-Mejía, R. G., Morf, J., Cairns, J., Román-Figueroa, A., Tenorio-Hernández, L., Poot-Hernández, A. C., Andrews, S., Várnai, C., Virk, B., Wingett, S. W., & Fraser, P.
Affiliations
  • Universidad Nacional Autónoma de México (MX)
  • Babraham Institute (GB)
  • Florida State University (US)
Corresponding author
Furlan-Magaril, Mayra
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2021-06-08
Volume
22
Issue
1
Pages
162-162
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/s13059-021-02374-3
PMC
PMC8185950
OpenAlex
W3167461954
Cited by
39
References
9
Citations by year
2026: 8 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 15 · 2021: 5
FWCI
3.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
  • Apollo
  • Apollo (cc-by)
  • ETH Zürich Research Collection (cc-by)
Funders
  • UNAM Technology Innovation and Research Support Program PAPIIT (IN207319)
  • Consejo Nacional de Ciencia y Tecnología (15758)
  • FP7 Ideas: European Research Council (259743)
  • Biotechnology and Biological Sciences Research Council (BB/J004480/1)
  • European Research Council (340152)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
Keywords
circadian gene expression, 3D genome organization, topologically associating domains, promoter capture Hi-C, liver, core clock genes, nuclear receptors, transcription factor binding sites, chromatin interactions, temporal resolution
MeSH terms
Animals, Base Sequence, Biological Clocks, Chromatin, Circadian Rhythm, Enhancer Elements, Genetic, Gene Expression Regulation, Liver, Male, Mice, Inbred C57BL, Models, Genetic, Promoter Regions, Genetic, Time Factors, Transcription, Genetic, Genome, Mice

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