Differentiation-dependent changes in lamin B1 dynamics and lamin B receptor localization

层粘蛋白B1动力学和层粘蛋白B受体定位的分化依赖性变化

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作者:Chase C Wesley ,Daniel L Levy

Abstract

The nuclear lamina serves important roles in chromatin organization and structural support, and lamina mutations can result in laminopathies. Less is known about how nuclear lamina structure changes during cellular differentiation-changes that may influence gene regulation. We examined the structure and dynamics of the nuclear lamina in human-induced pluripotent stem cells (iPSCs) and differentiated germ layer cells, focusing on lamin B1. We report that lamin B1 dynamics generally increase as iPSCs differentiate, especially in mesoderm and ectoderm, and that lamin B receptor (LBR) partially redistributes from the nucleus to cytoplasm in mesoderm. Knocking down LBR in iPSCs led to an increase in lamin B1 dynamics, a change that was not observed for ELYS, emerin, or lamin B2 knockdown. LBR knockdown also affected expression of differentiation markers. These data suggest that differentiation-dependent tethering of lamin B1 either directly by LBR or indirectly via LBR-chromatin associations impacts gene expression.

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