Lamin A/C and Emerin depletion impacts chromatin organization and dynamics in the interphase nucleus

Devika Ranade,Kundan Sengupta,Roopali Pradhan,Muhunden Jayakrishnan,Sushmitha Hegde

doi:10.1186/s12860-019-0192-5

Devika Ranade, Kundan Sengupta + Show 3 more

Open Access

https://doi.org/10.1186/s12860-019-0192-5

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Abstract

BackgroundNuclear lamins are type V intermediate filament proteins that maintain nuclear structure and function. Furthermore, Emerin - an interactor of Lamin A/C, facilitates crosstalk between the cytoskeleton and the nucleus as it also interacts with actin and Nuclear Myosin 1 (NM1).ResultsHere we show that the depletion of Lamin A/C or Emerin, alters the localization of the nuclear motor protein - Nuclear Myosin 1 (NM1) that manifests as an increase in NM1 foci in the nucleus and are rescued to basal levels upon the combined knockdown of Lamin A/C and Emerin. Furthermore, Lamin A/C-Emerin co-depletion destabilizes cytoskeletal organization as it increases actin stress fibers. This further impinges on nuclear organization, as it enhances chromatin mobility more toward the nuclear interior in Lamin A/C-Emerin co-depleted cells. This enhanced chromatin mobility was restored to basal levels either upon inhibition of Nuclear Myosin 1 (NM1) activity or actin depolymerization. In addition, the combined loss of Lamin A/C and Emerin alters the otherwise highly conserved spatial positions of chromosome territories. Furthermore, knockdown of Lamin A/C or Lamin A/C-Emerin combined, deregulates expression levels of a candidate subset of genes. Amongst these genes, both KLK10 (Chr.19, Lamina Associated Domain (LAD+)) and MADH2 (Chr.18, LAD-) were significantly repressed, while BCL2L12 (Chr.19, LAD-) is de-repressed. These genes differentially reposition with respect to the nuclear envelope.ConclusionsTaken together, these studies underscore a remarkable interplay between Lamin A/C and Emerin in modulating cytoskeletal organization of actin and NM1 that impinges on chromatin dynamics and function in the interphase nucleus.

Highlights

Nuclear lamins are type V intermediate filament proteins that maintain nuclear structure and function
B type lamins interact with Lamin B Receptor (LBR) and HP1α associated with heterochromatin [29], while A type lamins interact with proteins associated with both hetero and euchromatin namely LAP2α, Emerin and BANF1 [30,31,32]
Lamin A/C or Emerin knockdown increases nuclear myosin 1 (NM1) foci in the nucleus Emerin is localized in the cytoplasm and at the nuclear envelope of cells [76, 77]

Summary

Introduction

Nuclear lamins are type V intermediate filament proteins that maintain nuclear structure and function. Lamins are type V intermediate filament proteins, enriched at the nuclear envelope that regulate nuclear structure-function relationships and are required for maintaining the non-random organization of chromosome territories [5]. While B type lamins are expressed in all cells, Lamin A/ C expression is lower in stem cells and increases as cells differentiate [9,10,11,12] In addition to their localization and abundance at the nuclear envelope, a sub-fraction of both A and B type Lamins exist in the nucleoplasm [13,14,15,16,17,18,19,20]. LADs bound by B type lamins are proximal to the nuclear envelope, while those bound by A type lamins exist both at the nuclear periphery and interior respectively [38, 39]

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