Microbiology and Immunology Department, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Life Sci Alliance. 2023 Jul 6;6(9). doi: 10.26508/lsa.202201683. Print 2023 Sep.
Members of the BTB-ZF transcription factor family regulate the immune system. Our laboratory identified that family member Zbtb20 contributes to the differentiation, recall responses, and metabolism of CD8 T cells. Here, we report a characterization of the transcriptional and epigenetic signatures controlled by Zbtb20 at single-cell resolution during the effector and memory phases of the CD8 T cell response. Without Zbtb20, transcriptional programs associated with memory CD8 T cell formation were up-regulated throughout the CD8 T response. A signature of open chromatin was associated with genes controlling T cell activation, consistent with the known impact on differentiation. In addition, memory CD8 T cells lacking Zbtb20 were characterized by open chromatin regions with overrepresentation of AP-1 transcription factor motifs and elevated RNA- and protein-level expressions of the corresponding AP-1 components. Finally, we describe motifs and genomic annotations from the DNA targets of Zbtb20 in CD8 T cells identified by cleavage under targets and release under nuclease (CUT&RUN). Together, these data establish the transcriptional and epigenetic networks contributing to the control of CD8 T cell responses by Zbtb20.
BTB-ZF 转录因子家族成员调节免疫系统。我们实验室发现，该家族成员 Zbtb20 有助于 CD8 T 细胞的分化、回忆反应和代谢。在这里，我们报告了在 CD8 T 细胞反应的效应和记忆阶段，Zbtb20 控制的转录和表观遗传特征在单细胞分辨率下的特征。没有 Zbtb20，与记忆 CD8 T 细胞形成相关的转录程序在整个 CD8 T 反应中被上调。开放染色质的特征与控制 T 细胞激活的基因有关，这与已知的分化影响一致。此外，缺乏 Zbtb20 的记忆 CD8 T 细胞的特征是具有代表性的 AP-1 转录因子基序的开放染色质区域，以及相应的 AP-1 成分的 RNA 和蛋白质水平表达升高。最后，我们描述了通过在目标下切割和在核酸酶下释放（CUT&RUN）在 CD8 T 细胞中鉴定的 Zbtb20 的 DNA 靶标中的基序和基因组注释。总之，这些数据建立了转录和表观遗传网络，有助于 Zbtb20 控制 CD8 T 细胞反应。
