美国索尔克生物研究所Ye Zheng、Diana C. Hargreaves等研究人员合作，利用全基因组CRISPR筛选发现非经典核小体重塑复合物BAF在Foxp3表达和调节性T细胞功能中的作用。2020年7月7日，《免疫》在线发表了这项成果。

Title: A Genome-wide CRISPR Screen Reveals a Role for the Non-Canonical Nucleosome-Remodeling BAF Complex in Foxp3 Expression and Regulatory T Cell Function

Author: Chin-San Loo, Jovylyn Gatchalian, Yuqiong Liang, Mathias Leblanc, Mingjun Xie, Josephine Ho, Bhargav Venkatraghavan, Diana C. Hargreaves, Ye Zheng

Issue&Volume: 2020-07-07

Abstract: Regulatory T (Treg) cells play a pivotal role in suppressing auto-reactive T cells and maintaining immune homeostasis. Treg cell development and function are dependent on the transcription factor Foxp3. Here, we performed a genome-wide CRISPR loss-of-function screen to identify Foxp3 regulators in mouse primary Treg cells. Foxp3 regulators were enriched in genes encoding subunits of the SWI/SNF nucleosome-remodeling and SAGA chromatin-modifying complexes. Among the three SWI/SNF-related complexes, the Brd9-containing non-canonical (nc) BAF complex promoted Foxp3 expression, whereas the PBAF complex was repressive. Chemical-induced degradation of Brd9 led to reduced Foxp3 expression and reduced Treg cell function in vitro. Brd9 ablation compromised Treg cell function in inflammatory disease and tumor immunity in vivo. Furthermore, Brd9 promoted Foxp3 binding and expression of a subset of Foxp3 target genes. Our findings provide an unbiased analysis of the genetic networks regulating Foxp3 and reveal ncBAF as a target for therapeutic manipulation of Treg cell function.

DOI: 10.1016/j.immuni.2020.06.011

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30266-1