Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells
Kuznetsov NV1, Almuzzaini B2,3, Kritikou JS1, Baptista MAP1,4, Oliveira MMS1, Keszei M1, Snapper SB5, Percipalle P2,6,7, Westerberg LS8.
1 Department of Microbiology Tumor and Cell biology, Karolinska Institutet, Stockholm, 171 77, Sweden.
2 Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 171 77, Sweden.
3 King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences Medical Genomic Research Department, MNGHA, Riyadh, Saudi Arabia.
4 Institute for Virology and Immunobiology, University of Würzburg, 97078, Würzburg, Germany.
5 Gastroenterology Division, Children’s Hospital, Harvard Medical School, Boston, MA, 02115, USA.
6 Biology Program, New York University Abu Dhabi (NYUAD), P.O. Box 129188, Abu Dhabi, United Arab Emirates.
7 Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91, Stockholm, Sweden.
8 Department of Microbiology Tumor and Cell biology, Karolinska Institutet, Stockholm, 171 77, Sweden. Lisa.Westerberg@ki.se.
Year of Publication:
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.
We performed WASp chromatin immunoprecipitation and deep sequencing (ChIP-seq) in thymocytes and spleen CD4+ T cells.
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.
These data place nuclear WASp in proximity with TCF1 and TCF12, essential factors for T cell development.