Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells
Abstract Background The Wiskott–Aldrich syndrome protein (WASp) family of actin-nucleating factors are present in the cytoplasm and in the nucleus. The role of nuclear WASp for T cell development remains incompletely defined. Methods We performed WASp chromatin immunoprecipitation and deep sequencin...
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| Format: | Article |
| Language: | English |
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BMC
2017-10-01
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| Series: | Genome Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s13073-017-0481-6 |
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| author | Nikolai V. Kuznetsov Bader Almuzzaini Joanna S. Kritikou Marisa A. P. Baptista Mariana M. S. Oliveira Marton Keszei Scott B. Snapper Piergiorgio Percipalle Lisa S. Westerberg |
| author_facet | Nikolai V. Kuznetsov Bader Almuzzaini Joanna S. Kritikou Marisa A. P. Baptista Mariana M. S. Oliveira Marton Keszei Scott B. Snapper Piergiorgio Percipalle Lisa S. Westerberg |
| author_sort | Nikolai V. Kuznetsov |
| collection | DOAJ |
| description | Abstract Background The Wiskott–Aldrich syndrome protein (WASp) family of actin-nucleating factors are present in the cytoplasm and in the nucleus. The role of nuclear WASp for T cell development remains incompletely defined. Methods We performed WASp chromatin immunoprecipitation and deep sequencing (ChIP-seq) in thymocytes and spleen CD4+ T cells. Results WASp was enriched at genic and intergenic regions and associated with the transcription start sites of protein-coding genes. Thymocytes and spleen CD4+ T cells showed 15 common WASp-interacting genes, including the gene encoding T cell factor (TCF)12. WASp KO thymocytes had reduced nuclear TCF12 whereas thymocytes expressing constitutively active WASpL272P and WASpI296T had increased nuclear TCF12, suggesting that regulated WASp activity controlled nuclear TCF12. We identify a putative DNA element enriched in WASp ChIP-seq samples identical to a TCF1-binding site and we show that WASp directly interacted with TCF1 in the nucleus. Conclusions These data place nuclear WASp in proximity with TCF1 and TCF12, essential factors for T cell development. |
| first_indexed | 2024-12-17T09:10:33Z |
| format | Article |
| id | doaj.art-0361830f057d4d0aa6483dff822ab402 |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-12-17T09:10:33Z |
| publishDate | 2017-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-0361830f057d4d0aa6483dff822ab4022022-12-21T21:55:14ZengBMCGenome Medicine1756-994X2017-10-019111810.1186/s13073-017-0481-6Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cellsNikolai V. Kuznetsov0Bader Almuzzaini1Joanna S. Kritikou2Marisa A. P. Baptista3Mariana M. S. Oliveira4Marton Keszei5Scott B. Snapper6Piergiorgio Percipalle7Lisa S. Westerberg8Department of Microbiology Tumor and Cell biology, Karolinska InstitutetDepartment of Cell and Molecular Biology, Karolinska InstitutetDepartment of Microbiology Tumor and Cell biology, Karolinska InstitutetDepartment of Microbiology Tumor and Cell biology, Karolinska InstitutetDepartment of Microbiology Tumor and Cell biology, Karolinska InstitutetDepartment of Microbiology Tumor and Cell biology, Karolinska InstitutetGastroenterology Division, Children’s Hospital, Harvard Medical SchoolDepartment of Cell and Molecular Biology, Karolinska InstitutetDepartment of Microbiology Tumor and Cell biology, Karolinska InstitutetAbstract Background The Wiskott–Aldrich syndrome protein (WASp) family of actin-nucleating factors are present in the cytoplasm and in the nucleus. The role of nuclear WASp for T cell development remains incompletely defined. Methods We performed WASp chromatin immunoprecipitation and deep sequencing (ChIP-seq) in thymocytes and spleen CD4+ T cells. Results WASp was enriched at genic and intergenic regions and associated with the transcription start sites of protein-coding genes. Thymocytes and spleen CD4+ T cells showed 15 common WASp-interacting genes, including the gene encoding T cell factor (TCF)12. WASp KO thymocytes had reduced nuclear TCF12 whereas thymocytes expressing constitutively active WASpL272P and WASpI296T had increased nuclear TCF12, suggesting that regulated WASp activity controlled nuclear TCF12. We identify a putative DNA element enriched in WASp ChIP-seq samples identical to a TCF1-binding site and we show that WASp directly interacted with TCF1 in the nucleus. Conclusions These data place nuclear WASp in proximity with TCF1 and TCF12, essential factors for T cell development.http://link.springer.com/article/10.1186/s13073-017-0481-6WASpT cellsChIP-seqWiskott–Aldrich syndromeTCF1TCF12 |
| spellingShingle | Nikolai V. Kuznetsov Bader Almuzzaini Joanna S. Kritikou Marisa A. P. Baptista Mariana M. S. Oliveira Marton Keszei Scott B. Snapper Piergiorgio Percipalle Lisa S. Westerberg Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells Genome Medicine WASp T cells ChIP-seq Wiskott–Aldrich syndrome TCF1 TCF12 |
| title | Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells |
| title_full | Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells |
| title_fullStr | Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells |
| title_full_unstemmed | Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells |
| title_short | Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells |
| title_sort | nuclear wiskott aldrich syndrome protein co regulates t cell factor 1 mediated transcription in t cells |
| topic | WASp T cells ChIP-seq Wiskott–Aldrich syndrome TCF1 TCF12 |
| url | http://link.springer.com/article/10.1186/s13073-017-0481-6 |
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