Role of dynamic nuclear deformation on genomic architecture reorganization.

Junichi Takeda,Fumitaka Osakada,Ryo Kobayashi,Sungrim Seirin-Lee,Takashi Yamamoto,Satoshi Tashiro,Hiroshi Ochiai,Alexandre V Morozov

doi:10.1371/journal.pcbi.1007289

Junichi Takeda, Fumitaka Osakada + Show 6 more

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https://doi.org/10.1371/journal.pcbi.1007289

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Abstract

Higher-order genomic architecture varies according to cell type and changes dramatically during differentiation. One of the remarkable examples of spatial genomic reorganization is the rod photoreceptor cell differentiation in nocturnal mammals. The inverted nuclear architecture found in adult mouse rod cells is formed through the reorganization of the conventional architecture during terminal differentiation. However, the mechanisms underlying these changes remain largely unknown. Here, we found that the dynamic deformation of nuclei via actomyosin-mediated contractility contributes to chromocenter clustering and promotes genomic architecture reorganization during differentiation by conducting an in cellulo experiment coupled with phase-field modeling. Similar patterns of dynamic deformation of the nucleus and a concomitant migration of the nuclear content were also observed in rod cells derived from the developing mouse retina. These results indicate that the common phenomenon of dynamic nuclear deformation, which accompanies dynamic cell behavior, can be a universal mechanism for spatiotemporal genomic reorganization.

Highlights

In a typical nucleus during interphase, the long strands of genomic DNA are organized in a cell-type specific spatial architecture that plays an important role in DNA transcription, repair, and replication [1]
We found that dynamic nuclear deformation provides a driving force for long-range migration and aggressive clustering of chromocenters, which induces nuclear architecture reorganization
Heterochromatin and CC are tethered by lamin B receptor (LBR) and/or lamins A/C (LamA/C) protein localized at the nuclear membrane [2]

Summary

Introduction

In a typical nucleus during interphase, the long strands of genomic DNA are organized in a cell-type specific spatial architecture that plays an important role in DNA transcription, repair, and replication [1]. In the cell precursors of rod photoreceptors, heterochromatin and the chromocenters (CCs, mainly consisting of highly-condensed centromere heterochromatic regions) are located at the nuclear periphery, whereas euchromatin is localized deeper inside the nucleus. This nuclear conformation becomes inverted during differentiation into mature rod photoreceptor cells. The CCs gather into a single cluster at the nuclear center and are surrounded by heterochromatin, while euchromatin shifts to the nuclear periphery (Fig 1A)

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