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Background <p>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.</p> Results <p>Here, we show that ALFIN-LIKE (AL) proteins are responsible for H2A.Z gene body patterning in&#xa0;<i>Arabidopsis</i>. AL proteins encode H3K4me3-binding PHD domains, and by ChIP-seq, we confirm preferential binding of AL5 to H3K4me3 over H3K4me1/2&#xa0;<i>in planta</i>. We observe a global reduction in H2A.Z in&#xa0;<i>al</i>&#xa0;septuple mutants (<i>al7m</i>), 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,&#xa0;<i>al7m</i>&#xa0;mutants show severe developmental abnormalities and upregulation of H2A.Z gene body-enriched responsive genes.</p> Conclusions <p>Therefore, we propose a model whereby AL proteins direct gene body enrichment of H2A.Z by recruiting SWR1 to H3K4me3-containing responsive genes.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月21日

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

摘要

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.