SWR1-Independent Association of H2A.Z to the LINC Complex Promotes Meiotic Chromosome Motion.

Sara González-Arranz,Neem J Patel,Jennifer M Gardner,Jesús A Carballo,Zulin Yu,Pedro A San-Segundo,Beatriz Santos,Jonna Heldrich,Andreas Hochwagen,Sue L Jaspersen

doi:10.3389/fcell.2020.594092

Abstract

The H2A.Z histone variant is deposited into the chromatin by the SWR1 complex, affecting multiple aspects of meiosis. We describe here a SWR1-independent localization of H2A.Z at meiotic telomeres and the centrosome. We demonstrate that H2A.Z colocalizes and interacts with Mps3, the SUN component of the linker of nucleoskeleton, and cytoskeleton (LINC) complex that spans the nuclear envelope and links meiotic telomeres to the cytoskeleton, promoting meiotic chromosome movement. H2A.Z also interacts with the meiosis-specific Ndj1 protein that anchors telomeres to the nuclear periphery via Mps3. Telomeric localization of H2A.Z depends on Ndj1 and the N-terminal domain of Mps3. Although telomeric attachment to the nuclear envelope is maintained in the absence of H2A.Z, the distribution of Mps3 is altered. The velocity of chromosome movement during the meiotic prophase is reduced in the htz1Δ mutant lacking H2A.Z, but it is unaffected in swr1Δ cells. We reveal that H2A.Z is an additional LINC-associated factor that contributes to promote telomere-driven chromosome motion critical for error-free gametogenesis.

Highlights

Meiosis is a special form of cell division that lies at the heart of gametogenesis in most sexually reproducing organisms
We found that H2A.Z and Ndj1 interact at the nuclear envelope (NE), as manifested by the reconstitution of fluorescence from the Venus variant of the yellow fluorescent protein (VenusYFP) at the nuclear periphery in meiotic cells simultaneously expressing both moieties of VenusYFP fused to H2A.Z and Ndj1 (HTZ1-VC-kanMX6 containing the N-terminal (VN) and NDJ1-C-terminal moiety of the Venus fluorescent protein (VC), respectively) (Figures 3A,D)
The H2A.Z histone variant is involved in a myriad of biological processes, both in mitotic and meiotic cells, that rely on its chromatin incorporation at particular genomic positions where the ATP-dependent chromatin remodeler SWR1 is responsible for replacing H2A–H2B dimers to H2A.Z–H2B at nucleosomes (Billon and Cote, 2013)

Summary

Introduction

Meiosis is a special form of cell division that lies at the heart of gametogenesis in most sexually reproducing organisms. Chromatin remodeling events, including histone posttranslational modifications and incorporation of histone variants, play important roles in several processes during meiotic development (Brachet et al, 2012; Yamada and Ohta, 2013; Crichton et al, 2014; Ontoso et al, 2014; Yamada et al, 2018a). H2A.Z is a variant of the canonical H2A histone that is incorporated into the chromatin by the action of the ATP-dependent SWR1 remodeling complex. H2A.Z participates in a number of fundamental biological processes in vegetative cells including transcription regulation, chromatin silencing, DNA damage response, and chromosome segregation (Morillo-Huesca et al, 2010; Adkins et al, 2013; Billon and Cote, 2013; Weber and Henikoff, 2014). Many of the meiotic functions mentioned above for H2A.Z rely on its chromatin deposition mediated by the SWR1 complex

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Conclusion