Loss of Lamin A Changes the Spatial Organization of the Genome

Lamin A protein plays a major role in maintaining the structural organization and function of the chromatin in the nucleus. We lately hypothesized that lamin A can link two strands of DNA to one another, and act as a nano-linker.

Here we used an imaging method called fluorescence in situ hybridization (FISH). It enables to visualize small or large pieces of DNA in the nucleus and study the three-dimensional organization of entire chromosomes. A chromosome is a large piece of DNA of about ~100 Mega base-pairs and a human cell contains 46 chromosomes. Using “whole chromosome painting” together with FISH, it enables to have a close glimpse of the organization of the genome in the nucleus.

We found that in normal cells, the chromosomes are organized in a compact manner and each one is packed in a compact volume called chromosome territory. In contrast, when we deplete lamin A from the cell, the chromosomes lose their organization, they become loose and spread in a large area in the nucleus. Our results, therefore, provide insight about the role played by lamin A in maintaining chromatin structure. It strongly supports our hypothesis that lamin A forms DNA cross-links, thereby turning the long DNA polymer into an organized and well-maintained structure.