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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,...

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Autores principales: Org, Tõnis, Chignola, Francesca, Hetényi, Csaba, Gaetani, Massimiliano, Rebane, Ana, Liiv, Ingrid, Maran, Uko, Mollica, Luca, Bottomley, Matthew J, Musco, Giovanna, Peterson, Pärt
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2261226/
https://www.ncbi.nlm.nih.gov/pubmed/18292755
http://dx.doi.org/10.1038/embor.2008.11
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author Org, Tõnis
Chignola, Francesca
Hetényi, Csaba
Gaetani, Massimiliano
Rebane, Ana
Liiv, Ingrid
Maran, Uko
Mollica, Luca
Bottomley, Matthew J
Musco, Giovanna
Peterson, Pärt
author_facet Org, Tõnis
Chignola, Francesca
Hetényi, Csaba
Gaetani, Massimiliano
Rebane, Ana
Liiv, Ingrid
Maran, Uko
Mollica, Luca
Bottomley, Matthew J
Musco, Giovanna
Peterson, Pärt
author_sort Org, Tõnis
collection PubMed
description 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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spelling pubmed-22612262008-04-09 The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression Org, Tõnis Chignola, Francesca Hetényi, Csaba Gaetani, Massimiliano Rebane, Ana Liiv, Ingrid Maran, Uko Mollica, Luca Bottomley, Matthew J Musco, Giovanna Peterson, Pärt EMBO Rep Scientific Report 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. Nature Publishing Group 2008-04 2008-02-22 /pmc/articles/PMC2261226/ /pubmed/18292755 http://dx.doi.org/10.1038/embor.2008.11 Text en Copyright © 2008, European Molecular Biology Organization http://creativecommons.org/licenses/by-nc-nd/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation or the creation of derivative works without specific permission.
spellingShingle Scientific Report
Org, Tõnis
Chignola, Francesca
Hetényi, Csaba
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
title The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression
title_full The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression
title_fullStr The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression
title_full_unstemmed The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression
title_short The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression
title_sort autoimmune regulator phd finger binds to non-methylated histone h3k4 to activate gene expression
topic Scientific Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2261226/
https://www.ncbi.nlm.nih.gov/pubmed/18292755
http://dx.doi.org/10.1038/embor.2008.11
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