Unmodified Histone H3K4 and DNA-Dependent Protein Kinase Recruit Autoimmune Regulator to Target Genes

REFERENCES

• Aaltonen J, Björses P, Sandkuijl L, Perheentupa J, Peltonen L. 1994. An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21. Nat. Genet. 8:83–87.
   PubMed Web of Science ®Google Scholar
• Abramson J, Giraud M, Benoist C, Mathis D. 2010. Aire's partners in the molecular control of immunological tolerance. Cell 140:123–135.
   PubMed Web of Science ®Google Scholar
• Anderson MS, Su MA. 2011. Aire and T cell development. Curr. Opin. Immunol. 23:198–206.
   PubMedGoogle Scholar
• Bottomley MJ, et al. 2001. The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation. Nat. Struct. Biol. 8:626–633.
   PubMedGoogle Scholar
• Chen BPC, et al. 2005. Cell cycle dependence of DNA-dependent protein kinase phosphorylation in response to DNA double strand breaks. J. Biol. Chem. 280:14709–14715.
   PubMed Web of Science ®Google Scholar
• Chi P, Allis CD, Wang GG. 2010. Covalent histone modifications–miswritten, misinterpreted and mis-erased in human cancers. Nat. Rev. Cancer 10:457–469.
   PubMed Web of Science ®Google Scholar
• Chignola F, et al. 2009. The solution structure of the first PHD finger of autoimmune regulator in complex with non-modified histone H3 tail reveals the antagonistic role of H3R2 methylation. Nucleic Acids Res. 37:2951–2961.
   PubMed Web of Science ®Google Scholar
• Ciccia A, Elledge SJ. 2010. The DNA damage response: making it safe to play with knives. Mol. Cell 40:179–204.
   PubMed Web of Science ®Google Scholar
• Derbinski J, et al. 2005. Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels. J. Exp. Med. 202:33–45.
   PubMed Web of Science ®Google Scholar
• Dobbs TA, Tainer JA, Lees-Miller SP. 2010. A structural model for regulation of NHEJ by DNA-PKcs autophosphorylation. DNA Repair 9:1307–1314.
   PubMed Web of Science ®Google Scholar
• Douglas P, et al. 2007. The DNA-dependent protein kinase catalytic subunit is phosphorylated in vivo on threonine 3950, a highly conserved amino acid in the protein kinase domain. Mol. Cell. Biol. 27:1581–1591.
   PubMed Web of Science ®Google Scholar
• Dynan WS, Yoo S. 1998. Interaction of Ku protein and DNA-dependent protein kinase catalytic subunit with nucleic acids. Nucleic Acids Res. 26:1551–1559.
   PubMedGoogle Scholar
• Finnish-German Consortium APECED. 1997. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat. Genet. 17:399–403.
   PubMedGoogle Scholar
• Gillard GO, Farr AG. 2006. Features of medullary thymic epithelium implicate postnatal development in maintaining epithelial heterogeneity and tissue-restricted antigen expression. J. Immunol. 176:5815–5824.
   PubMed Web of Science ®Google Scholar
• Gotter J, Kyewski B. 2004. Regulating self-tolerance by deregulating gene expression. Curr. Opin. Immunol. 16:741–745.
   PubMedGoogle Scholar
• Haffner MC, De Marzo AM, Meeker AK, Nelson WG, Yegnasubramanian S. 2011. Transcription-induced DNA double strand breaks: both oncogenic force and potential therapeutic target? Clin. Cancer Res. 17:3858–3864.
   PubMed Web of Science ®Google Scholar
• Halonen M, et al. 2004. APECED-causing mutations in AIRE reveal the functional domains of the protein. Hum. Mutat. 23:245–257.
   PubMedGoogle Scholar
• Ilmarinen T, et al. 2005. Functional analysis of SAND mutations in AIRE supports dominant inheritance of the G228W mutation. Hum. Mutat. 26:322–331.
   PubMed Web of Science ®Google Scholar
• Jiang H, Peterlin BM. 2008. Differential chromatin looping regulates CD4 expression in immature thymocytes. Mol. Cell. Biol. 28:907–912.
   PubMed Web of Science ®Google Scholar
• Johnnidis JB, et al. 2005. Chromosomal clustering of genes controlled by the aire transcription factor. Proc. Natl. Acad. Sci. U. S. A. 102:7233–7238.
   PubMed Web of Science ®Google Scholar
• Ju B-G, et al. 2006. A topoisomerase IIbeta-mediated dsDNA break required for regulated transcription. Science 312:1798–1802.
   PubMed Web of Science ®Google Scholar
• Kamine J, Subramanian T, Chinnadurai G. 1991. Sp1-dependent activation of a synthetic promoter by human immunodeficiency virus type 1 Tat protein. Proc. Natl. Acad. Sci. U. S. A. 88:8510–8514.
   PubMedGoogle Scholar
• Koh AS, Kingston RE, Benoist C, Mathis D. 2010. Global relevance of Aire binding to hypomethylated lysine-4 of histone-3. Proc. Natl. Acad. Sci. U. S. A. 107:13016–13021.
   PubMedGoogle Scholar
• Koh AS, et al. 2008. Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunity. Proc. Natl. Acad. Sci. U. S. A. 105:15878–15883.
   PubMed Web of Science ®Google Scholar
• Kumar PG, et al. 2001. The autoimmune regulator (AIRE) is a DNA-binding protein. J. Biol. Chem. 276:41357–41364.
   PubMedGoogle Scholar
• Kyewski B, Klein L. 2006. A central role for central tolerance. Annu. Rev. Immunol. 24:571–606.
   PubMed Web of Science ®Google Scholar
• Leahy JJJ, et al. 2004. Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries. Bioorg. Med. Chem. Lett. 14:6083–6087.
   PubMed Web of Science ®Google Scholar
• Liiv I, et al. 2008. DNA-PK contributes to the phosphorylation of AIRE: importance in transcriptional activity. Biochim. Biophys. Acta 1783:74–83.
   PubMed Web of Science ®Google Scholar
• Mathis D, Benoist C. 2009. AIRE. Annu. Rev. Immunol. 27:287–312.
   PubMed Web of Science ®Google Scholar
• Mizuochi T, Kasai M, Kokuho T, Kakiuchi T, Hirokawa K. 1992. Medullary but not cortical thymic epithelial cells present soluble antigens to helper T cells. J. Exp. Med. 175:1601–1605.
   PubMedGoogle Scholar
• Mo X, Dynan WS. 2002. Subnuclear localization of Ku protein: functional association with RNA polymerase II elongation sites. Mol. Cell. Biol. 22:8088–8099.
   PubMedGoogle Scholar
• Muslimović A, Nyström S, Gao Y, Hammarsten O. 2009. Numerical analysis of etoposide induced DNA breaks. PLoS One 4:e5859.
   PubMedGoogle Scholar
• Nagamine K, et al. 1997. Positional cloning of the APECED gene. Nat. Genet. 17:393–398.
   PubMed Web of Science ®Google Scholar
• Org T, et al. 2008. The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression. EMBO Rep. 9:370–376.
   PubMedGoogle Scholar
• Org T, et al. 2009. AIRE activated tissue specific genes have histone modifications associated with inactive chromatin. Hum. Mol. Genet. 18:4699–4710.
   PubMed Web of Science ®Google Scholar
• Oven I, et al. 2007. AIRE recruits P-TEFb for transcriptional elongation of target genes in medullary thymic epithelial cells. Mol. Cell. Biol. 27:8815–8823.
   PubMed Web of Science ®Google Scholar
• Peña PV, et al. 2006. Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2. Nature 442:100–103.
   PubMed Web of Science ®Google Scholar
• Peterlin BM, Price DH. 2006. Controlling the elongation phase of transcription with P-TEFb. Mol. Cell 23:297–305.
   PubMed Web of Science ®Google Scholar
• Peterson P, Org T, Rebane A. 2008. Transcriptional regulation by AIRE: molecular mechanisms of central tolerance. Nat. Rev. Immunol. 8:948–957.
   PubMed Web of Science ®Google Scholar
• Peterson SR, et al. 1997. Characterization of two DNA double-stranded break repair-deficient cell lines that express inactive DNA-dependent protein kinase catalytic subunits. J. Biol. Chem. 272:10227–10231.
   PubMedGoogle Scholar
• Purohit S, Kumar PG, Laloraya M, She J-X. 2005. Mapping DNA-binding domains of the autoimmune regulator protein. Biochem. Biophys. Res. Commun. 327:939–944.
   PubMedGoogle Scholar
• Taube R, Lin X, Irwin D, Fujinaga K, Peterlin BM. 2002. Interaction between P-TEFb and the C-terminal domain of RNA polymerase II activates transcriptional elongation from sites upstream or downstream of target genes. Mol. Cell. Biol. 22:321–331.
   PubMed Web of Science ®Google Scholar
• Taverna SD, Li H, Ruthenburg AJ, Allis CD, Patel DJ. 2007. How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat. Struct. Mol. Biol. 14:1025–1040.
   PubMed Web of Science ®Google Scholar
• Tykocinski L-O, et al. 2010. Epigenetic regulation of promiscuous gene expression in thymic medullary epithelial cells. Proc. Natl. Acad. Sci. U. S. A. 107:19426–19431.
   PubMedGoogle Scholar
• Weterings E, Chen DJ. 2007. DNA-dependent protein kinase in nonhomologous end joining: a lock with multiple keys? J. Cell Biol. 179:183–186.
   PubMed Web of Science ®Google Scholar
• Wong RHF, et al. 2009. A role of DNA-PK for the metabolic gene regulation in response to insulin. Cell 136:1056–1072.
   PubMed Web of Science ®Google Scholar
• Zumer K, Plemenitas A, Saksela K, Peterlin BM. 2011. Patient mutation in AIRE disrupts P-TEFb binding and target gene transcription. Nucleic Acids Res. 39:7908–7919.
   PubMedGoogle Scholar