The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression.
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.
Org
Tõnis
T
Molecular Pathology, University of Tartu, Tartu 50411, Estonia.
Chignola
Francesca
F
Hetényi
Csaba
C
Gaetani
Massimiliano
M
Rebane
Ana
A
Liiv
Ingrid
I
Maran
Uko
U
Mollica
Luca
L
Bottomley
Matthew J
MJ
Musco
Giovanna
G
Peterson
Pärt
P
D002151:Calorimetry; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D016884:Polyendocrinopathies, Autoimmune / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000096927:AIRE Protein
D006657:Histones; D014157:Transcription Factors; D000096927:AIRE Protein