核 Wiskott-Aldrich 综合征蛋白在 T 细胞中共同调节 T 细胞因子 1 介导的转录。

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

机构信息

Department of Microbiology Tumor and Cell biology, Karolinska Institutet, Stockholm, 171 77, Sweden.

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 171 77, Sweden.

出版信息

Genome Med. 2017 Oct 27;9(1):91. doi: 10.1186/s13073-017-0481-6.

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 WASp and WASp 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.

背景

Wiskott-Aldrich 综合征蛋白（WASp）家族的肌动蛋白成核因子存在于细胞质和细胞核中。核 WASp 对 T 细胞发育的作用尚未完全确定。

方法

我们在胸腺细胞和脾脏 CD4 T 细胞中进行了 WASp 染色质免疫沉淀和深度测序（ChIP-seq）。

结果

WASp 在基因和基因间区域富集，并与蛋白质编码基因的转录起始位点相关。胸腺细胞和脾脏 CD4 T 细胞显示出 15 个共同的 WASp 相互作用基因，包括编码 T 细胞因子（TCF）12 的基因。WASp KO 胸腺细胞中核 TCF12 减少，而表达组成性激活 WASp 和 WASp 的胸腺细胞中核 TCF12 增加，表明受调控的 WASp 活性控制核 TCF12。我们确定了一个在 WASp ChIP-seq 样本中富集的假定 DNA 元件，该元件与 TCF1 结合位点相同，并且我们表明 WASp 在核内直接与 TCF1 相互作用。