Gene-rich chromosomal regions are preferentially localized in the lamin B deficient nuclear blebs of atypical progeria cells

Nucleus
Katrin Bercht PfleghaarRobert D Goldman

Abstract

More than 20 mutations in the gene encoding A-type lamins (LMNA) cause progeria, a rare premature aging disorder. The major pathognomonic hallmarks of progeria cells are seen as nuclear deformations or blebs that are related to the redistribution of A- and B-type lamins within the nuclear lamina. However, the functional significance of these progeria-associated blebs remains unknown. We have carried out an analysis of the structural and functional consequences of progeria-associated nuclear blebs in dermal fibroblasts from a progeria patient carrying a rare point mutation p.S143F (C428T) in lamin A/C. These blebs form microdomains that are devoid of major structural components of the nuclear envelope (NE)/lamina including B-type lamins and nuclear pore complexes (NPCs) and are enriched in A-type lamins. Using laser capture microdissection and comparative genomic hybridization (CGH) analyses, we show that, while these domains are devoid of centromeric heterochromatin and gene-poor regions of chromosomes, they are enriched in gene-rich chromosomal regions. The active form of RNA polymerase II is also greatly enriched in blebs as well as nascent RNA but the nuclear co-activator SKIP is significantly reduced in blebs compared to ot...Continue Reading

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Citations

Sep 8, 2016·Frontiers in Genetics·Jérôme D Robin, Frédérique Magdinier
Jan 30, 2018·Journal of the European Academy of Dermatology and Venereology : JEADV·A G GranaP Chicre Bandeira de Melo
Aug 3, 2016·Disease Models & Mechanisms·Dido CarreroCarlos López-Otín
Aug 1, 2019·Molecular Biology of the Cell·Andrew D StephensJohn F Marko
Aug 18, 2020·The FEBS Journal·Agathe MarcelotSophie Zinn-Justin
Jul 22, 2020·Annual Review of Cell and Developmental Biology·John Maciejowski, Emily M Hatch
Nov 11, 2020·BMC Bioinformatics·Priyojit DasRachel Patton McCord
Mar 20, 2019·Current Opinion in Cell Biology·Andrew D StephensJohn F Marko
Mar 14, 2017·Trends in Cell Biology·Pragya ShahJan Lammerding

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Methods Mentioned

BETA
FCS
transfection
Fluorescence

Software Mentioned

Zeiss Isis CGH

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