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

BMC Molecular and Cell Biology

Devika Ranade¹  Roopali Pradhan¹  Muhunden Jayakrishnan¹  Kundan Sengupta¹  Sushmitha Hegde¹ 

[1] 0000 0004 1764 2413, grid.417959.7, Indian Institute of Science Education and Research (IISER)-Pune, Dr. Homi Bhabha Road, Biology, Room#B-216, 1st Floor, Main Building, Pashan, 411008, Pune, Maharashtra, India;

关键词: Nucleus;    Chromosome territories;    Lamin A/C;    Emerin;    Nuclear myosin 1;    Actin;   

DOI  :  10.1186/s12860-019-0192-5

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY