TY - JOUR
T1 - The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression
AU - Org, Tõnis
AU - Chignola, Francesca
AU - Hetényi, Csaba
AU - Gaetani, Massimiliano
AU - Rebane, Ana
AU - Liiv, Ingrid
AU - Maran, Uko
AU - Mollica, Luca
AU - Bottomley, Matthew J.
AU - Musco, Giovanna
AU - Peterson, Pärt
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
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U2 - 10.1038/embor.2008.11
DO - 10.1038/embor.2008.11
M3 - Article
C2 - 18292755
AN - SCOPUS:45849137524
SN - 1469-221X
VL - 9
SP - 370
EP - 376
JO - EMBO Reports
JF - EMBO Reports
IS - 4
ER -