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与H3K4me3结合的类ALFIN蛋白招募SWR1以进行H2A.Z在基因体上的沉积。

H3K4me3 binding ALFIN-LIKE proteins recruit SWR1 for gene-body deposition of H2A.Z.

作者信息

Xu Linhao, Wang Yafei, Li Xueying, Hu Qin, Adamkova Vanda, Xu Junjie, Harris C Jake, Ausin Israel

机构信息

Department of Plant Sciences, University of Cambridge, Cambridge, CB2 3EA, UK.

State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, College of Life Sciences and Institute of Future Agriculture, Northwest A&F University, Yangling, 712100, Shaanxi, China.

出版信息

Genome Biol. 2025 May 21;26(1):137. doi: 10.1186/s13059-025-03605-7.

DOI:10.1186/s13059-025-03605-7

PMID:40399998

Abstract

BACKGROUND

The H2A.Z histone variant is highly enriched over gene bodies, playing an essential role in several genome-templated processes, including transcriptional regulation and epigenetic patterning across eukaryotes. Deposition of H2A.Z is mediated by the SWR1 remodeling complex. How SWR1 is directed to gene bodies is largely unknown.

RESULTS

Here, we show that ALFIN-LIKE (AL) proteins are responsible for H2A.Z gene body patterning in Arabidopsis. AL proteins encode H3K4me3-binding PHD domains, and by ChIP-seq, we confirm preferential binding of AL5 to H3K4me3 over H3K4me1/2 in planta. We observe a global reduction in H2A.Z in al septuple mutants (al7m), especially over H3K4me3-enriched genic regions. While MBD9 recruits SWR1 to nucleosome-free regions, ALs act non-redundantly with MBD9 for deposition of H2A.Z. Notably, al7m mutants show severe developmental abnormalities and upregulation of H2A.Z gene body-enriched responsive genes.

CONCLUSIONS

Therefore, we propose a model whereby AL proteins direct gene body enrichment of H2A.Z by recruiting SWR1 to H3K4me3-containing responsive genes.

摘要

背景

H2A.Z组蛋白变体在基因体上高度富集，在包括转录调控和真核生物表观遗传模式形成在内的多个基因组模板化过程中发挥着重要作用。H2A.Z的沉积由SWR1重塑复合体介导。SWR1如何被引导至基因体在很大程度上尚不清楚。

结果

在这里，我们表明拟南芥中的类ALFIN（AL）蛋白负责H2A.Z在基因体上的模式形成。AL蛋白编码与H3K4me3结合的PHD结构域，通过染色质免疫沉淀测序（ChIP-seq），我们证实了在植物中AL5对H3K4me3的结合优先于H3K4me1/2。我们观察到在al七重突变体（al7m）中H2A.Z整体减少，尤其是在富含H3K4me3的基因区域。虽然MBD9将SWR1招募到无核小体区域，但AL蛋白与MBD9在H2A.Z的沉积中发挥非冗余作用。值得注意的是，al7m突变体表现出严重的发育异常以及H2A.Z基因体富集的响应基因的上调。