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Transcriptional regulator PRDM12 is essential for human pain perception

A Corrigendum to this article was published on 29 July 2015

This article has been updated


Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments1,2. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal3,4. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP)5,6. Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis7,8. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory neurogenesis and may hold promise as a target for new pain therapeutics9,10.

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Figure 1: Identification of mutations in PRDM12.
Figure 2: Phenotype of affected individuals with PRDM12 mutations.
Figure 3: A role for Prdm12 in sensory neuron development.
Figure 4: Consequences of PRDM12 mutations.

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  • 08 July 2015

    In the version of this article initially published, there was an error with the affiliations for author Roman Chrast. His correct affiliations are: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. The error has been corrected in the HTML and PDF versions of the article.


  1. Merskey, H. & Watson, G.D. The lateralisation of pain. Pain 7, 271–280 (1979).

    Article  CAS  PubMed  Google Scholar 

  2. Bennett, D.L. & Woods, C.G. Painful and painless channelopathies. Lancet Neurol. 13, 587–599 (2014).

    Article  CAS  PubMed  Google Scholar 

  3. Stewart, W.F., Ricci, J.A., Chee, E., Morganstein, D. & Lipton, R. Lost productive time and cost due to common pain conditions in the US workforce. J. Am. Med. Assoc. 290, 2443–2454 (2003).

    Article  CAS  Google Scholar 

  4. Breivik, H., Collett, B., Ventafridda, V., Cohen, R. & Gallacher, D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur. J. Pain 10, 287–333 (2006).

    Article  PubMed  Google Scholar 

  5. Goldberg, Y.P. et al. Human Mendelian pain disorders: a key to discovery and validation of novel analgesics. Clin. Genet. 82, 367–373 (2012).

    Article  CAS  PubMed  Google Scholar 

  6. Holmes, D. Anti-NGF painkillers back on track? Nat. Rev. Drug Discov. 11, 337–338 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. Hohenauer, T. & Moore, A.W. The Prdm family: expanding roles in stem cells and development. Development 139, 2267–2282 (2012).

    Article  CAS  PubMed  Google Scholar 

  8. Kinameri, E. et al. Prdm proto-oncogene transcription factor family expression and interaction with the Notch-Hes pathway in mouse neurogenesis. PLoS One 3, e3859 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Crow, M., Denk, F. & McMahon, S.B. Genes and epigenetic processes as prospective pain targets. Genome Med. 5, 12 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Denk, F. & McMahon, S.B. Chronic pain: emerging evidence for the involvement of epigenetics. Neuron 73, 435–444 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cox, J.J. et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature 444, 894–898 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Leipold, E. et al. A de novo gain-of-function mutation in SCN11A causes loss of pain perception. Nat. Genet. 45, 1399–1404 (2013).

    Article  CAS  PubMed  Google Scholar 

  13. Indo, Y. et al. Mutations in the TRKA/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis. Nat. Genet. 13, 485–488 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. Einarsdottir, E. et al. A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception. Hum. Mol. Genet. 13, 799–805 (2004).

    Article  CAS  PubMed  Google Scholar 

  15. Carvalho, O.P. et al. A novel NGF mutation clarifies the molecular mechanism and extends the phenotypic spectrum of the HSAN5 neuropathy. J. Med. Genet. 48, 131–135 (2011).

    Article  CAS  PubMed  Google Scholar 

  16. Albrecht, A. & Mundlos, S. The other trinucleotide repeat: polyalanine expansion disorders. Curr. Opin. Genet. Dev. 15, 285–293 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. Hughes, J. et al. Mechanistic insight into the pathology of polyalanine expansion disorders revealed by a mouse model for X linked hypopituitarism. PLoS Genet. 9, e1003290 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dubin, A.E. & Patapoutian, A. Nociceptors: the sensors of the pain pathway. J. Clin. Invest. 120, 3760–3772 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ochoa, J. & Mair, W.G. The normal sural nerve in man. I. Ultrastructure and numbers of fibres and cells. Acta Neuropathol. 13, 197–216 (1969).

    Article  CAS  PubMed  Google Scholar 

  20. Hall, B.K. The neural crest and neural crest cells: discovery and significance for theories of embryonic organization. J. Biosci. 33, 781–793 (2008).

    Article  PubMed  Google Scholar 

  21. Ma, Q., Fode, C., Guillemot, F. & Anderson, D.J. Neurogenin1 and neurogenin2 control two distinct waves of neurogenesis in developing dorsal root ganglia. Genes Dev. 13, 1717–1728 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Chambers, S.M. et al. Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors. Nat. Biotechnol. 30, 715–720 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Young, G.T. et al. Characterizing human stem cell-derived sensory neurons at the single-cell level reveals their ion channel expression and utility in pain research. Mol. Ther. 22, 1530–1543 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zannino, D.A., Downes, G.B. & Sagerström, C.G. Prdm12b specifies the p1 progenitor domain and reveals a role for V1 interneurons in swim movements. Dev. Biol. 390, 247–260 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Schlosser, G. Induction and specification of cranial placodes. Dev. Biol. 294, 303–351 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. Moore, A.W., Jan, L.Y. & Jan, Y.N. Hamlet, a binary genetic switch between single- and multiple- dendrite neuron morphology. Science 297, 1355–1358 (2002).

    Article  CAS  PubMed  Google Scholar 

  27. Rossi, C.C., Kaji, T. & Artinger, K.B. Transcriptional control of Rohon-Beard sensory neuron development at the neural plate border. Dev. Dyn. 238, 931–943 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Endo, K. et al. Chromatin modification of Notch targets in olfactory receptor neuron diversification. Nat. Neurosci. 15, 224–233 (2012).

    Article  CAS  Google Scholar 

  29. Chittka, A., Nitarska, J., Grazini, U. & Richardson, W.D. Transcription factor positive regulatory domain 4 (PRDM4) recruits protein arginine methyltransferase 5 (PRMT5) to mediate histone arginine methylation and control neural stem cell proliferation and differentiation. J. Biol. Chem. 287, 42995–43006 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yang, C.M. & Shinkai, Y. Prdm12 is induced by retinoic acid and exhibits anti-proliferative properties through the cell cycle modulation of P19 embryonic carcinoma cells. Cell Struct. Funct. 38, 197–206 (2013).

    Article  PubMed  Google Scholar 

  31. Hu, X.L., Wang, Y. & Shen, Q. Epigenetic control on cell fate choice in neural stem cells. Protein Cell 3, 278–290 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tan, S.L. et al. Essential roles of the histone methyltransferase ESET in the epigenetic control of neural progenitor cells during development. Development 139, 3806–3816 (2012).

    Article  CAS  PubMed  Google Scholar 

  33. Jobe, E.M., McQuate, A.L. & Zhao, X. Crosstalk among epigenetic pathways regulates neurogenesis. Front. Neurosci. 6, 59 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Boshnjaku, V. et al. Epigenetic regulation of sensory neurogenesis in the dorsal root ganglion cell line ND7 by folic acid. Epigenetics 6, 1207–1216 (2011).

    Article  CAS  PubMed  Google Scholar 

  35. Amir, R.E. et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23, 185–188 (1999).

    Article  CAS  PubMed  Google Scholar 

  36. Kleefstra, T. et al. Loss-of-function mutations in euchromatin histone methyl transferase 1 (EHMT1) cause the 9q34 subtelomeric deletion syndrome. Am. J. Hum. Genet. 79, 370–377 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Klein, C.J. et al. Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat. Genet. 43, 595–600 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Jakovcevski, M. & Akbarian, S. Epigenetic mechanisms in neurological disease. Nat. Med. 18, 1194–1204 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Huang, S., Shao, G. & Liu, L. The PR domain of the Rb-binding zinc finger protein RIZ1 is a protein binding interface and is related to the SET domain functioning in chromatin-mediated gene expression. J. Biol. Chem. 273, 15933–15939 (1998).

    Article  CAS  PubMed  Google Scholar 

  40. Rozenblatt-Rosen, O. et al. The C-terminal SET domains of ALL-1 and TRITHORAX interact with the INI1 and SNR1 proteins, components of the SWI/SNF complex. Proc. Natl. Acad. Sci. USA 95, 4152–4157 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cui, X. et al. Association of SET domain and myotubularin-related proteins modulates growth control. Nat. Genet. 18, 331–337 (1998).

    Article  CAS  PubMed  Google Scholar 

  42. Cardoso, C. et al. Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein. Hum. Mol. Genet. 7, 679–684 (1998).

    Article  CAS  PubMed  Google Scholar 

  43. Doppler, K., Werner, C. & Sommer, C. Disruption of nodal architecture in skin biopsies of patients with demyelinating neuropathies. J. Peripher. Nerv. Syst. 18, 168–176 (2013).

    Article  CAS  PubMed  Google Scholar 

  44. Nicholas, A.K. et al. The molecular landscape of ASPM mutations in primary microcephaly. J. Med. Genet. 46, 249–253 (2009).

    Article  CAS  PubMed  Google Scholar 

  45. Choi, Y., Sims, G.E., Murphy, S., Miller, J.R. & Chan, A.P. Predicting the functional effect of amino acid substitutions and indels. PLoS One 7, e46688 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ng, P.C. & Henikoff, S. Accounting for human polymorphisms predicted to affect protein function. Genome Res. 12, 436–446 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Schwarz, J.M., Cooper, D.N., Schuelke, M. & Seelow, D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat. Methods 11, 361–362 (2014).

    Article  CAS  PubMed  Google Scholar 

  48. Adzhubei, I.A. et al. A method and server for predicting damaging missense mutations. Nat. Methods 7, 248–249 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Wong, K.C. & Zhang, Z. SNPdryad: predicting deleterious non-synonymous human SNPs using only orthologous protein sequences. Bioinformatics 30, 1112–1119 (2014).

    Article  CAS  PubMed  Google Scholar 

  50. Higuchi, R., Krummel, B. & Saiki, R. A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions. Nucleic Acids Res. 16, 7351–7367 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Grove, E.A., Tole, S., Limon, J., Yip, L. & Ragsdale, C.W. The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice. Development 125, 2315–2325 (1998).

    CAS  PubMed  Google Scholar 

  52. Stendel, C. et al. SH3TC2, a protein mutant in Charcot-Marie-Tooth neuropathy, links peripheral nerve myelination to endosomal recycling. Brain 133, 2462–2474 (2010).

    Article  PubMed  Google Scholar 

  53. Arnaud, E. et al. SH3TC2/KIAA1985 protein is required for proper myelination and the integrity of the node of Ranvier in the peripheral nervous system. Proc. Natl. Acad. Sci. USA 106, 17528–17533 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Nieuwkoop, P.D. & Faber, J. Normal Table of Xenopus Embryos (North-Holland, 1967).

  55. Harland, R.M. In situ hybridization: an improved whole-mount method for Xenopus embryos. Methods Cell Biol. 36, 685–695 (1991).

    Article  CAS  PubMed  Google Scholar 

  56. Sato, T., Sasai, N. & Sasai, Y. Neural crest determination by co-activation of Pax3 and Zic1 genes in Xenopus ectoderm. Development 132, 2355–2363 (2005).

    Article  CAS  PubMed  Google Scholar 

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The authors are grateful for the participation of the patients and their families in this study. The help of all contributing medical, technical and administrative staff is greatly appreciated. We thank S. Malik for her invaluable work with family A, J.R.P. Madrid and F. Axelrod for advice and discussion and M.F. Passarge for helpful suggestions on the text. D.L.H.B. is a senior Wellcome Clinical Scientist (ref. no. 095698z/11/z). This work was supported by Cambridge NIHR Biomedical Research Centre (Y.-C.C., F.S. and C.G.W.), Austrian Science Fond (P23223-B19 to M.A.-G.), the UK Medical Research Council (M.S.N. and S.S.S.), Association Belge contre les Maladies Neuromusculaires and EU FP7/2007-2013 (grant 2012-305121 (NEUROMICS) to J.B. and P.D.J.), Deutsche Forschungsgemeinschaft (CRC/SFB 1140 to C.B. and KU1587/4-1 to I. Kurth), Gebert-Rüf Stiftung (GRS-046/09 to R.C. and J.S.), and Friedrich-Baur Stiftung (J.S.).

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Authors and Affiliations



M.A.-G., Y.P., L.G.-N., W.H., R.M.W., J.M.H., U.M., M.B., D.P., C.M.R., K.v.A., C.F., G.K., M.A.M., J.C.M., S.M.M., A.D.I., U.B.J. and C.G.W. enrolled patients in the study and provided patient care. Y.P., L.G.-N., E.P., J.M.H., E.M.V., P.J.W., M.R.C., C.B., B.R., J.B., P.D.J., M.M.R., R.K., I. Kurth, C.G.W. and J.S. obtained DNA samples, skin biopsies and nerve biopsy specimens. Y.-C.C., M.A.-G., T.M.S., C.W., M.S., T.W., F.S., M.S.N., S.S.S., O.P.C., A.K.N., C.G.W. and J.S. carried out linkage analysis and PRDM12 mutation screening. Y.-C.C., M.Z., C. Samara, A.W.M., R.S. and R.C. performed expression studies on Prdm12. Y.-C.C., S.M., M.Z., C.W., R.S., M.D., C. Stendel, F.R., T.M. and J.S. assessed functional consequences of mutations in PRDM12. A.C.T., A.B.S., I. Katona, J.W. and D.L.H.B. analyzed skin biopsies from CIP patients. S.M. and T.M. performed experiments in Xenopus embryos. Y.-C.C., L.T.-Y.C. and G.T.Y. were responsible for experiments involving pluripotent stem cells. R.S. and J.S. carried out protein modeling. A.W.M., R.W., J.W., I. Kurth and D.L.H.B. gave critical advice. M.A.-G., C.G.W. and J.S. oversaw the project, participated in data analysis and directed and supervised the research. The manuscript was written by Y.-C.C., M.A.-G., C.G.W. and J.S. with input from other authors.

Corresponding authors

Correspondence to C Geoffrey Woods or Jan Senderek.

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The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Detection and segregation analysis of the PRDM12 mutations in CIP families.

Mutations segregate with the disease consistent with autosomal recessive inheritance. All affected probands are homozygous for the respective mutations. m: mutation; wt: wild type.

Supplementary Figure 2 Multiple sequence alignment of human PRDM12 and orthologous sequences.

Multiple protein sequence alignment generated with the program ClustalW. Sequence comparison showed that the PRDM12 missense mutations (red arrows) observed in patients with CIP affect amino acids that are identical in PRDM12 and its orthologs. Orange bar: PR/SET domain; blue bars: ZF motifs; green bar: poly-alanine tract.

Supplementary Figure 3 Distribution of PRDM12 poly-alanine tract lengths within different ethnic groups.

The length distribution of the PRDM12 poly-alanine tract showed a similar spectrum in different populations. The number of chromosomes analysed is given below the diagrams.

Supplementary Figure 4 Skin biopsy findings.

Skin biopsy from the lower lip, patient P7. (a) Dermal nerve fibres do not cross the dermal-epidermal border (dotted line). Staining with pan-neuronal marker PGP9.5, scale bar: 50 μm. (b) Dermal nerve containing myelinated fibres. Co-staining with PGP9.5 and myelin marker protein MBP; scale bar: 25 μm. (c) Innervation of sweat glands. Co-staining with PGP9.5 and VIP, a marker for a subpopulation of autonomic neurons; scale bar: 25 μm.

Supplementary Figure 5 Prdm12 expression in the peripheral nervous system.

(a) Prdm12 mRNA is contained in mouse dorsal root ganglia (DRG) but not in sympathetic ganglia (SG) at E13.5. Gapdh was used as loading control. A no reverse transcriptase control (No RT) was used to exclude amplification from genomic DNA. (b) Purified DRG neurons (obtained by treating DRG explant cultures with 5-Fluorouracil) but not cells from the mouse Schwann cell line (MSC80) express Prdm12. The purity of the cell preparation was proven by RT-PCR for the S100 gene (Schwann cell marker) and the identity of neurons was confirmed by RT-PCR for Tuj-1 (neuron-specific class III β-tubulin). E13.5 DRG tissue and liver were used as positive and negative controls, respectively.

Supplementary Figure 6 Electrophysiological properties of iPSC-derived sensory neurons and gene expression of hESC-derived sensory neurons.

(a) IPSC-derived sensory neurons (from a parallel culture of those used for RT-qPCR analysis in Fig. 3c) expressed tetrodotoxin (TTX)-resistant nociceptor ion channels (Nav1.8) after 52 days in culture demonstrating the cells utility as a model of human DRG neurons. Voltage-gated sodium currents were elicited in whole-cell voltage-clamp by voltage steps from -120 mV to 0 mV in the absence (control, black), presence (drug, red), and after washout (recovery, blue) of 500 nM TTX (scale bar, 10 nA and 25 ms). (b) The electrophysiological recording confirmed the membrane expression of nociceptor ion channels as a TTX-resistant sodium current (Nav1.8) was observed following TTX application (control=557.1±78.9 pA/pF, TTX (500 nM)=113.9±19.4 pA/pF, wash=486.4±62.2 pA/pF; n=5). (c) HESC-derived sensory neurons expressed PRDM12 during differentiation. PRDM12 expression was quantified by RT-qPCR and was found to peak at the neural crest specification stage of development (Day 9). The differentiated cells were shown to also express canonical markers of sensory neurons, NGF receptor NTRK1 and ion channel SCN9A, indicating cell specification into sensory neuron phenotype.

Supplementary Figure 7 PRDM12 expression in adult human tissues.

No PRDM12 expression was observed by RT-PCR using cDNA from various tissues and leukocytes (Clontech Human MTC Panel I and II, cat. no.: 636742 and 636743). Amplification of GAPDH was used to ensure integrity of the cDNA. Functionality of PRDM12 primers was tested with cDNA from human DRG.

Supplementary Figure 8 Prdm12 expression and knockdown in Xenopus embryos.

(a) Prdm12 expression overlapped with the sensory placode marker Islet1 (yellow and green arrowheads) but was absent from other cranial placodes such as lens (Six3). Whole-mount in situ hybridisation, lateral views of late tailbud-stage embryos (stage 26). Gene expression domains of cranial placodes (colored outlines) in Xenopus laevis are shown in the schematic drawing (lateral view, late tailbud stage (modified from25)). An asterisk marks Prdm12 expression in diencephalon. PN: expression in pronephros. (b) Inhibition of Myc-Prdm12 translation by specific morpholino. Embryos were co-injected with Myc-Prdm12 mRNA and Control MO (5, 10, 20 ng/embryo) or Prdm12 MO (5, 10, 20 ng/embryo) at 2-cell stage and protein extracts were obtained from 26-stage embryos. Western blotting analysis was performed with anti-Myc and anti-α-tubulin antibodies. (Note that in situ hybridisation is not suitable to measure Prdm12 knockdown as the morpholino affects protein translation but does not predictably change the rate of mRNA degradation.) (c) Knockdown of Prdm12 by Prdm12 MO only marginally affected lens placode markers Six3 and Pax6 and otic placode marker Pax8 in Xenopus embryos. Embryos injected with Control MO (20 ng/embryo) or Prdm12 MO (20 ng/embryo) were analyzed at late tailbud stage (stage 28) by whole-mount in situ hybridisation. For normal gene expression domains of cranial placodes see (a), PN: pronephros. The results were categorized and quantified (n40 alive embryos per condition). Differences between Control MO- and Prdm12 MO-treated embryos were assessed statistically: ns, not significant (two-sided Mann-Whitney U-test).

Supplementary Figure 9 Consequences of PRDM12 mutations.

(a) Effects of PRDM12 mutations on protein expression. Transfected missense mutant and wild-type mouse Myc-Prdm12 showed similar levels in COS-7 cells. Prdm12 signals were normalized to α-tubulin and GFP (transfection control). The graphs represent mean values of n independent experiments (biological replicates) and error bars represent SD. Differences between control (wild type) and Prdm12 mutants were assessed statistically: ns, not significant (Welch’s t-test). (b) Localisation in HEK-293T cells. Wild-type and missense mutant human HA-PRDM12 protein labelled nuclei in a diffuse pattern. (c) Co-immunoprecipitation of Prdm12 with G9a. Myc-Prdm12 and FLAG-G9a were expressed in COS-7 cells and immunoprecipitated using anti-Myc antibody. For quantification, bound G9a was normalized to Prdm12 protein amount in the IP fraction and the G9a protein amount in the cell lysate. The graphs represent mean values of n independent experiments (biological replicates), and error bars represent SD. Differences between control (wild type) and Prdm12 mutants were assessed statistically: ns, not significant (Welch’s t-test). (d) Chromatin fractionation of COS-7 cells transfected with human HA-PRDM12. Wild type and mutant PRDM12 appeared in both fractions. Alpha-tubulin (soluble fraction) and acetylated histone 3 (chromatin fraction) were used as controls to determine fraction purity.

Supplementary Figure 10 Prdm12-induced H3K9 dimethylation.

Animal cap cells from Xenopus embryos were co-microinjected with Myc-Prdm12 of Xenopus, mouse or human origin, Wnt8 and Chrd mRNA and cultured until mid-neurula stage (stage 15). A dose-dependent increase of H3K9me2 (compared to negative control) was observed between 0.5, 1 and 2 ng/embryo doses of Myc-Prdm12, irrespective of whether the frog protein or its mammalian orthologs were overexpressed.

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Chen, YC., Auer-Grumbach, M., Matsukawa, S. et al. Transcriptional regulator PRDM12 is essential for human pain perception. Nat Genet 47, 803–808 (2015).

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