The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression

Tõnis Org, Francesca Chignola, C. Hetényi, Massimiliano Gaetani, Ana Rebane, Ingrid Liiv, Uko Maran, Luca Mollica, Matthew J. Bottomley, Giovanna Musco, Pärt Peterson

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

Mutations in the gene autoimmune regulator (AIRE) cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. AIRE is expressed in thymic medullary epithelial cells, where it promotes the expression of tissue-restricted antigens. By the combined use of biochemical and biophysical methods, we show that AIRE selectively interacts with histone H3 through its first plant homeodomain (PHD) finger (AIRE-PHD1) and preferentially binds to non-methylated H3K4 (H3K4me0). Accordingly, in vivo AIRE binds to and activates promoters containing low levels of H3K4me3 in human embryonic kidney 293 cells. We conclude that AIRE-PHD1 is an important member of a newly identified class of PHD fingers that specifically recognize H3K4me0, thus providing a new link between the status of histone modifications and the regulation of tissue-restricted antigen expression in thymus.

Original languageEnglish
Pages (from-to)370-376
Number of pages7
JournalEMBO Reports
Volume9
Issue number4
DOIs
Publication statusPublished - 2008

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Gene expression
Histones
Fingers
Histone Code
Autoimmune Polyendocrinopathies
Tissue
Gene Expression
Antigens
Thymus
Regulator Genes
Thymus Gland
Genes
Epithelial Cells
Kidney
Mutation
Type 1 Autoimmune polyendocrinopathy syndrome

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression. / Org, Tõnis; Chignola, Francesca; Hetényi, C.; Gaetani, Massimiliano; Rebane, Ana; Liiv, Ingrid; Maran, Uko; Mollica, Luca; Bottomley, Matthew J.; Musco, Giovanna; Peterson, Pärt.

In: EMBO Reports, Vol. 9, No. 4, 2008, p. 370-376.

Research output: Contribution to journalArticle

Org, T, Chignola, F, Hetényi, C, Gaetani, M, Rebane, A, Liiv, I, Maran, U, Mollica, L, Bottomley, MJ, Musco, G & Peterson, P 2008, 'The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression', EMBO Reports, vol. 9, no. 4, pp. 370-376. https://doi.org/10.1038/embor.2008.11
Org, Tõnis ; Chignola, Francesca ; Hetényi, C. ; Gaetani, Massimiliano ; Rebane, Ana ; Liiv, Ingrid ; Maran, Uko ; Mollica, Luca ; Bottomley, Matthew J. ; Musco, Giovanna ; Peterson, Pärt. / The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression. In: EMBO Reports. 2008 ; Vol. 9, No. 4. pp. 370-376.
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