Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription (original) (raw)

Accession codes

Accessions

Gene Expression Omnibus

Data deposits

Sequencing data have been deposited in the Gene Expression Omnibus under accession GSE45914.

References

  1. Preitner, N. et al. The orphan nuclear receptor REV-ERBα controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110, 251–260 (2002)
    Article CAS Google Scholar
  2. Liu, A. C. et al. Redundant function of REV-ERBα and β and non-essential role for Bmal1 cycling in transcriptional regulation of intracellular circadian rhythms. PLoS Genet. 4, e1000023 (2008)
    Article Google Scholar
  3. Raspé, E. et al. Identification of Rev-erbα as a physiological repressor of apoC-III gene transcription. J. Lipid Res. 43, 2172–2179 (2002)
    Article Google Scholar
  4. Le Martelot, G. et al. REV-ERBα participates in circadian SREBP signaling and bile acid homeostasis. PLoS Biol. 7, e1000181 (2009)
    Article Google Scholar
  5. Gibbs, J. E. et al. The nuclear receptor REV-ERBα mediates circadian regulation of innate immunity through selective regulation of inflammatory cytokines. Proc. Natl Acad. Sci. USA 109, 582–587 (2012)
    Article ADS CAS Google Scholar
  6. Zamir, I. et al. A nuclear hormone receptor corepressor mediates transcriptional silencing by receptors with distinct repression domains. Mol. Cell. Biol. 16, 5458–5465 (1996)
    Article CAS Google Scholar
  7. Yin, L. & Lazar, M. A. The orphan nuclear receptor Rev-erbα recruits the N-CoR/histone deacetylase 3 corepressor to regulate the circadian Bmal1 gene. Mol. Endocrinol. 19, 1452–1459 (2005)
    Article CAS Google Scholar
  8. Feng, D. et al. A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism. Science 331, 1315–1319 (2011)
    Article ADS CAS Google Scholar
  9. Heintzman, N. D. et al. Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature 459, 108–112 (2009)
    Article ADS CAS Google Scholar
  10. Friedman, A. D. Transcriptional control of granulocyte and monocyte development. Oncogene 26, 6816–6828 (2007)
    Article CAS Google Scholar
  11. Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime _cis_-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2010)
    Article CAS Google Scholar
  12. Core, L. J., Waterfall, J. J. & Lis, J. T. Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322, 1845–1848 (2008)
    Article ADS CAS Google Scholar
  13. Schlaeger, T. M., Mikkola, H. K., Gekas, C., Helgadottir, H. B. & Orkin, S. H. Tie2Cre-mediated gene ablation defines the stem-cell leukemia gene (SCL/tal1)-dependent window during hematopoietic stem-cell development. Blood 105, 3871–3874 (2005)
    Article CAS Google Scholar
  14. Giguere, V. et al. Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors. Genes Dev. 8, 538–553 (1994)
    Article CAS Google Scholar
  15. Kim, T.-K. et al. Widespread transcription at neuronal activity-regulated enhancers. Nature 465, 182–187 (2010)
    Article ADS CAS Google Scholar
  16. Wang, D. et al. Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature 474, 390–394 (2011)
    Article CAS Google Scholar
  17. Hah, N. et al. A rapid, extensive, and transient transcriptional response to estrogen signaling in breast cancer cells. Cell 145, 622–634 (2011)
    Article CAS Google Scholar
  18. Bennett, C. F. & Swayze, E. E. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu. Rev. Pharmacol. Toxicol. 50, 259–293 (2010)
    Article CAS Google Scholar
  19. Guang, S. et al. Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription. Nature 465, 1097–1101 (2010)
    Article ADS CAS Google Scholar
  20. Gu, S. G. et al. Amplification of siRNA in Caenorhabditis elegans generates a transgenerational sequence-targeted histone H3 lysine 9 methylation footprint. Nature Genet. 44, 157–164 (2012)
    Article CAS Google Scholar
  21. Huang, W. et al. Coronin 2A mediates actin-dependent de-repression of inflammatory response genes. Nature 470, 414–418 (2011)
    Article ADS CAS Google Scholar
  22. Lai, F. et al. Activating RNAs associate with Mediator to enhance chromatin architecture and transcription. Nature 494, 497–501 (2013)
    Article ADS CAS Google Scholar
  23. Melo, C. A. et al. eRNAs are required for p53-dependent enhancer activity and gene transcription. Mol. Cell 49, 524–535 (2013)
    Article CAS Google Scholar
  24. Raal, F. J. et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet 375, 998–1006 (2010)
    Article CAS Google Scholar
  25. Cho, H. et al. Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β. Nature 485, 123–127 (2012)
    Article ADS CAS Google Scholar
  26. Saldanha, A. J. Java Treeview—extensible visualization of microarray data. Bioinformatics 20, 3246–3248 (2004)
    Article CAS Google Scholar
  27. Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010)
    Article CAS Google Scholar
  28. Schanke, J. T. Sequence inversion by Flip-PCR. Methods Mol. Biol. 67, 203–208 (1997)
    CAS PubMed Google Scholar
  29. Baker, B. F. et al. 2′-_O_-(2-Methoxy)ethyl-modified anti-intercellular adhesion molecule 1 (ICAM-1) oligonucleotides selectively increase the ICAM-1 mRNA level and inhibit formation of the ICAM-1 translation initiation complex in human umbilical vein endothelial cells. J. Biol. Chem. 272, 11994–12000 (1997)
    Article CAS Google Scholar
  30. Seth, P. P. et al. Design, synthesis and evaluation of constrained methoxyethyl (cMOE) and constrained ethyl (cEt) nucleoside analogs. Nucleic Acids Symp. Ser. 52, 553–554 (2008)
    Article CAS Google Scholar

Download references

Acknowledgements

We thank L. Bautista for assistance with figure preparation. These studies were supported by National Institutes of Health grants CA17390, U19DK62434, DK091183, DK063491, CA014195, DK057978, HL088093, HL105278 and CA52599. M.G.R. and R.M.E. are Investigators of the Howard Hughes Medical Institute. M.T.Y.L. is supported by the University of California, San Diego Medical Scientist Training Program T32 GM007198-37, and Genetics Training Program T32 GM008666, National Institute of General Medical Sciences. M.U.K. was supported by a LeDucq Foundation Fellowship. H.P.L. was supported by the Finnish Cultural Foundation, Instumentarium Foundation, The Paulo Foundation, Paavo Nurmi Foundation, Finnish Foundation for Cardiovascular Research, The Maud Kuistila Memorial Foundation and The Fulbright Center. These studies were also supported by grants from the Leona M. and Harry B. Helmsley Charitable Trust, Samuel Waxman Cancer Research Foundation, the Glenn Foundation for Medical Research, the Ellison Medical Foundation and Ipsen/Biomeasure.

Author information

Authors and Affiliations

  1. Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA,
    Michael T. Y. Lam, Hanna P. Lesch, David Gosselin, Sven Heinz, Yumiko Tanaka-Oishi, Christopher Benner, Minna U. Kaikkonen, Mika Kosaka, Cindy Y. Lee & Christopher K. Glass
  2. Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, 92037, California, USA
    Han Cho & Ronald M. Evans
  3. Isis Pharmaceuticals, Inc., 2855 Gazelle Court, Carlsbad, California 92010, USA,
    Aneeza S. Kim, Andy Watt & Tamar R. Grossman
  4. Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA,
    Michael G. Rosenfeld & Christopher K. Glass
  5. Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, 20815-6789, Maryland, USA
    Michael G. Rosenfeld & Ronald M. Evans

Authors

  1. Michael T. Y. Lam
    You can also search for this author inPubMed Google Scholar
  2. Han Cho
    You can also search for this author inPubMed Google Scholar
  3. Hanna P. Lesch
    You can also search for this author inPubMed Google Scholar
  4. David Gosselin
    You can also search for this author inPubMed Google Scholar
  5. Sven Heinz
    You can also search for this author inPubMed Google Scholar
  6. Yumiko Tanaka-Oishi
    You can also search for this author inPubMed Google Scholar
  7. Christopher Benner
    You can also search for this author inPubMed Google Scholar
  8. Minna U. Kaikkonen
    You can also search for this author inPubMed Google Scholar
  9. Aneeza S. Kim
    You can also search for this author inPubMed Google Scholar
  10. Mika Kosaka
    You can also search for this author inPubMed Google Scholar
  11. Cindy Y. Lee
    You can also search for this author inPubMed Google Scholar
  12. Andy Watt
    You can also search for this author inPubMed Google Scholar
  13. Tamar R. Grossman
    You can also search for this author inPubMed Google Scholar
  14. Michael G. Rosenfeld
    You can also search for this author inPubMed Google Scholar
  15. Ronald M. Evans
    You can also search for this author inPubMed Google Scholar
  16. Christopher K. Glass
    You can also search for this author inPubMed Google Scholar

Contributions

M.T.Y.L., S.H., C.B., A.W., T.R.G., M.G.R., R.M.E. and C.K.G. conceived the project and planned experiments, which were performed by M.T.Y.L., H.C., H.P.L., D.G., S.H., Y.T.-O., M.U.K., A.S.K., M.K. and C.Y.L., and analysed by M.T.Y.L., H.P.L., D.G., C.B. and C.K.G. The project was supervised by C.K.G., who wrote the manuscript with M.T.Y.L.

Corresponding author

Correspondence toChristopher K. Glass.

Ethics declarations

Competing interests

A.S.K., A.W. and T.R.G. are employees of Isis Pharmaceuticals.

Supplementary information

PowerPoint slides

Rights and permissions

About this article

Cite this article

Lam, M., Cho, H., Lesch, H. et al. Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription.Nature 498, 511–515 (2013). https://doi.org/10.1038/nature12209

Download citation