Cargando…

Forkhead Transcription Factor FOXP3 Upregulates CD25 Expression through Cooperation with RelA/NF-κB

Considerable evidence supports the prediction that CD25 is directly regulated by the forkhead transcription factor FOXP3. However, given that CD25 is normally upregulated in activated T cells, regardless of whether they express FOXP3, this issue has still to be definitively demonstrated. Here we des...

Descripción completa

Detalles Bibliográficos
Autores principales: Camperio, Cristina, Caristi, Silvana, Fanelli, Giorgia, Soligo, Marzia, Porto, Paola Del, Piccolella, Enza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483148/
https://www.ncbi.nlm.nih.gov/pubmed/23144749
http://dx.doi.org/10.1371/journal.pone.0048303
_version_ 1782247951075115008
author Camperio, Cristina
Caristi, Silvana
Fanelli, Giorgia
Soligo, Marzia
Porto, Paola Del
Piccolella, Enza
author_facet Camperio, Cristina
Caristi, Silvana
Fanelli, Giorgia
Soligo, Marzia
Porto, Paola Del
Piccolella, Enza
author_sort Camperio, Cristina
collection PubMed
description Considerable evidence supports the prediction that CD25 is directly regulated by the forkhead transcription factor FOXP3. However, given that CD25 is normally upregulated in activated T cells, regardless of whether they express FOXP3, this issue has still to be definitively demonstrated. Here we describe that FOXP3, induced by CD28 signals in human CD4(+)CD25(−) T lymphocytes, synergizes with RelA on a regulatory region of Cd25 promoter to mediate the transcriptional activation of Cd25 gene. We found that a striking feature of this regulatory region is the presence of a κB site and of two tandem copies of a non-consensus FOXP3 binding site separated at 5′ ends by 19 nucleotides that allow FOXP3 and RelA binding to DNA and their physical interaction. The occupancy of the two FOXP3 binding sites in conjunction with RelA binding site occupancy allows FOXP3 to function as a positive activator of Cd25 gene. Indeed mutations of both FOXP3 binding sites such as mutation of κB site on Cd25 promoter abolished FOXP3 activatory functions. Moreover, FOXP3 mutation ΔE251, that compromises FOXP3 homotypic interactions, failed to trans activate Cd25 promoter, suggesting that both FOXP3 DNA binding and dimerization are required to trans activate Cd25 promoter. These findings identify a novel mechanism by which RelA and FOXP3 cooperate to mediate transcriptional regulation of target genes and characterize a region on Cd25 promoter where FOXP3 dimer could bridge intramolecularly two DNA sites and trans activate Cd25 gene.
format Online
Article
Text
id pubmed-3483148
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-34831482012-11-09 Forkhead Transcription Factor FOXP3 Upregulates CD25 Expression through Cooperation with RelA/NF-κB Camperio, Cristina Caristi, Silvana Fanelli, Giorgia Soligo, Marzia Porto, Paola Del Piccolella, Enza PLoS One Research Article Considerable evidence supports the prediction that CD25 is directly regulated by the forkhead transcription factor FOXP3. However, given that CD25 is normally upregulated in activated T cells, regardless of whether they express FOXP3, this issue has still to be definitively demonstrated. Here we describe that FOXP3, induced by CD28 signals in human CD4(+)CD25(−) T lymphocytes, synergizes with RelA on a regulatory region of Cd25 promoter to mediate the transcriptional activation of Cd25 gene. We found that a striking feature of this regulatory region is the presence of a κB site and of two tandem copies of a non-consensus FOXP3 binding site separated at 5′ ends by 19 nucleotides that allow FOXP3 and RelA binding to DNA and their physical interaction. The occupancy of the two FOXP3 binding sites in conjunction with RelA binding site occupancy allows FOXP3 to function as a positive activator of Cd25 gene. Indeed mutations of both FOXP3 binding sites such as mutation of κB site on Cd25 promoter abolished FOXP3 activatory functions. Moreover, FOXP3 mutation ΔE251, that compromises FOXP3 homotypic interactions, failed to trans activate Cd25 promoter, suggesting that both FOXP3 DNA binding and dimerization are required to trans activate Cd25 promoter. These findings identify a novel mechanism by which RelA and FOXP3 cooperate to mediate transcriptional regulation of target genes and characterize a region on Cd25 promoter where FOXP3 dimer could bridge intramolecularly two DNA sites and trans activate Cd25 gene. Public Library of Science 2012-10-29 /pmc/articles/PMC3483148/ /pubmed/23144749 http://dx.doi.org/10.1371/journal.pone.0048303 Text en © 2012 Camperio et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Camperio, Cristina
Caristi, Silvana
Fanelli, Giorgia
Soligo, Marzia
Porto, Paola Del
Piccolella, Enza
Forkhead Transcription Factor FOXP3 Upregulates CD25 Expression through Cooperation with RelA/NF-κB
title Forkhead Transcription Factor FOXP3 Upregulates CD25 Expression through Cooperation with RelA/NF-κB
title_full Forkhead Transcription Factor FOXP3 Upregulates CD25 Expression through Cooperation with RelA/NF-κB
title_fullStr Forkhead Transcription Factor FOXP3 Upregulates CD25 Expression through Cooperation with RelA/NF-κB
title_full_unstemmed Forkhead Transcription Factor FOXP3 Upregulates CD25 Expression through Cooperation with RelA/NF-κB
title_short Forkhead Transcription Factor FOXP3 Upregulates CD25 Expression through Cooperation with RelA/NF-κB
title_sort forkhead transcription factor foxp3 upregulates cd25 expression through cooperation with rela/nf-κb
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483148/
https://www.ncbi.nlm.nih.gov/pubmed/23144749
http://dx.doi.org/10.1371/journal.pone.0048303
work_keys_str_mv AT camperiocristina forkheadtranscriptionfactorfoxp3upregulatescd25expressionthroughcooperationwithrelanfkb
AT caristisilvana forkheadtranscriptionfactorfoxp3upregulatescd25expressionthroughcooperationwithrelanfkb
AT fanelligiorgia forkheadtranscriptionfactorfoxp3upregulatescd25expressionthroughcooperationwithrelanfkb
AT soligomarzia forkheadtranscriptionfactorfoxp3upregulatescd25expressionthroughcooperationwithrelanfkb
AT portopaoladel forkheadtranscriptionfactorfoxp3upregulatescd25expressionthroughcooperationwithrelanfkb
AT piccolellaenza forkheadtranscriptionfactorfoxp3upregulatescd25expressionthroughcooperationwithrelanfkb