Lamin A/C modulates spatial organization and function of the Hsp70 gene locus via Nuclear Myosin I (NM1)

Abstract

Nuclear structure-function is tightly regulated, especially during heat shock. Typically, heat shock activates molecular chaperones that prevent protein misfolding and preserve genome integrity. However, the molecular mechanisms that regulate nuclear structure-function relationships during heat shock remain unclear. Here we show that Lamin A/C is required for heat shock mediated transcriptional induction of Hsp70 gene locus. Interestingly, Lamin A/C regulates redistribution of Nuclear Myosin I (NM1) into the nucleus upon heat shock, and depletion of either Lamin A/C or NM1 abrogates heat shock induced repositioning of Hsp70 gene locus away from the nuclear envelope. Lamins and NM1 also regulate spatial positioning of the SC35 speckles - important nuclear landmarks that modulates Hsp70 gene locus expression upon heat shock. This suggests an intricate crosstalk between nuclear lamins, NM1 and SC35 organization in modulating transcriptional responses of the Hsp70 gene locus during heat shock. Taken together, this study unravels a novel role for Lamin A/C in the regulation of the spatial dynamics and function of the Hsp70 gene locus upon heat shock, via the nuclear motor protein - NM1.