Nuclear Wiskott-Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells

Genome Medicine
Nikolai V KuznetsovLisa S Westerberg

Abstract

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.

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Citations

Jul 4, 2019·Scandinavian Journal of Immunology·Liang ZhangXiaodong Zhao
Oct 11, 2020·Cells·Magdalena IzdebskaAlina Grzanka
Dec 19, 2017·The Journal of Allergy and Clinical Immunology·Koustav SarkarYatin M Vyas
Aug 24, 2021·Frontiers in Cell and Developmental Biology·Julien RecordLisa S Westerberg

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Methods Mentioned

BETA
GTPases
nuclear
immunoprecipitation
ChIP
co-IP
ChIP-seq
electrophoresis
PCR
DamID
histone acetylation

Software Mentioned

ImageJ
SICER
ImageQuant
Adobe Photoshop
TRANSFAC®
GraphPad Prism
Openlab
ImageQuant LAS 4000
MACS Model Analysis
ChIPseek

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