美国斯隆凯特林研究所Alexander Y. Rudensky、Joris van der Veeken等研究人员合作发现,转录因子Foxp3通过调整反式作用的中间因子来塑造调节性T细胞的身份。2020年11月10日,国际知名学术期刊《免疫》在线发表了这一成果。
Title: The Transcription Factor Foxp3 Shapes Regulatory T Cell Identity by Tuning the Activity of trans-Acting Intermediaries
Author: Joris van der Veeken, Ariella Glasner, Yi Zhong, Wei Hu, Zhong-Min Wang, Regina Bou-Puerto, Louis-Marie Charbonnier, Talal A. Chatila, Christina S. Leslie, Alexander Y. Rudensky
Issue&Volume: 2020-11-10
Abstract: Regulatory T (Treg) cell identity is defined by the lineage-specifying transcriptionfactor (TF) Foxp3. Here we examined mechanisms of Foxp3 function by leveraging naturallyoccurring genetic variation in wild-derived inbred mice, which enables the identificationof DNA sequence motifs driving epigenetic features. Chromatin accessibility, TF binding,and gene expression patterns in resting and activated subsets of Treg cells, conventionalCD4 T cells, and cells expressing a Foxp3 reporter null allele revealed that the majority of Foxp3-dependent changes occurredat sites not bound by Foxp3. Chromatin accessibility of these indirect Foxp3 targetsdepended on the presence of DNA binding motifs for other TFs, including TCF1. Foxp3expression correlated with decreased TCF1 and reduced accessibility of TCF1-boundchromatin regions. Deleting one copy of the Tcf7 gene recapitulated Foxp3-dependent negative regulation of chromatin accessibility.Thus, Foxp3 defines Treg cell identity in a largely indirect manner by fine-tuningthe activity of other major chromatin remodeling TFs such as TCF1.
DOI: 10.1016/j.immuni.2020.10.010
Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30451-9
Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
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