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拟南芥 TRB 蛋白通过招募 JMJ14 来发挥 H3K4me3 去甲基化的功能。

Arabidopsis TRB proteins function in H3K4me3 demethylation by recruiting JMJ14.

机构信息

Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, CA, 90095, USA.

Instituto de Biología Molecular y Celular de Plantas (IBMCP), CSIC-Universitat Politècnica de València, 46022, Valencia, Spain.

出版信息

Nat Commun. 2023 Mar 28;14(1):1736. doi: 10.1038/s41467-023-37263-9.

Abstract

Arabidopsis telomeric repeat binding factors (TRBs) can bind telomeric DNA sequences to protect telomeres from degradation. TRBs can also recruit Polycomb Repressive Complex 2 (PRC2) to deposit tri-methylation of H3 lysine 27 (H3K27me3) over certain target loci. Here, we demonstrate that TRBs also associate and colocalize with JUMONJI14 (JMJ14) and trigger H3K4me3 demethylation at some loci. The trb1/2/3 triple mutant and the jmj14-1 mutant show an increased level of H3K4me3 over TRB and JMJ14 binding sites, resulting in up-regulation of their target genes. Furthermore, tethering TRBs to the promoter region of genes with an artificial zinc finger (TRB-ZF) successfully triggers target gene silencing, as well as H3K27me3 deposition, and H3K4me3 removal. Interestingly, JMJ14 is predominantly recruited to ZF off-target sites with low levels of H3K4me3, which is accompanied with TRB-ZFs triggered H3K4me3 removal at these loci. These results suggest that TRB proteins coordinate PRC2 and JMJ14 activities to repress target genes via H3K27me3 deposition and H3K4me3 removal.

摘要

拟南芥端粒重复结合因子(TRBs)可以结合端粒 DNA 序列,保护端粒免受降解。TRBs 还可以募集 Polycomb Repressive Complex 2(PRC2),在某些靶标基因上沉积 H3 赖氨酸 27 三甲基化(H3K27me3)。在这里,我们证明 TRBs 还与 JUMONJI14(JMJ14)相关联并共定位,并在一些基因座上触发 H3K4me3 去甲基化。trb1/2/3 三重突变体和 jmj14-1 突变体在 TRB 和 JMJ14 结合位点上显示出更高水平的 H3K4me3,导致其靶基因的上调。此外,将 TRBs 锚定在具有人工锌指(TRB-ZF)的基因启动子区域,成功地触发了靶基因沉默以及 H3K27me3 的沉积和 H3K4me3 的去除。有趣的是,JMJ14 主要募集到具有低水平 H3K4me3 的 ZF 脱靶位点,这伴随着 TRB-ZF 在这些基因座上触发的 H3K4me3 去除。这些结果表明,TRB 蛋白通过 H3K27me3 沉积和 H3K4me3 去除来协调 PRC2 和 JMJ14 活性来抑制靶基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4468/10049986/513e68a9c8d2/41467_2023_37263_Fig1_HTML.jpg

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