Role Of Nuclear Lamina Research Articles

Genome-wide maps of nucleolus interactions reveal distinct layers of repressive chromatin domains

Eukaryotic chromosomes are folded into hierarchical domains, forming functional compartments. Nuclear periphery and nucleolus are two nuclear landmarks contributing to repressive chromosome architecture. However, while the role of nuclear lamina (NL) in genome organization has been well documented, the function of the nucleolus remains under-investigated due to the lack of methods for the identification of nucleolar associated domains (NADs). Here we have established DamID- and HiC-based methodologies to generate accurate genome-wide maps of NADs in embryonic stem cells (ESCs) and neural progenitor cells (NPCs), revealing layers of genome compartmentalization with distinct, repressive chromatin states based on the interaction with the nucleolus, NL, or both. NADs show higher H3K9me2 and lower H3K27me3 content than regions exclusively interacting with NL. Upon ESC differentiation into NPCs, chromosomes around the nucleolus acquire a more compact, rigid architecture with neural genes moving away from nucleoli and becoming unlocked for later activation. Further, histone modifications and the interaction strength within A and B compartments of NADs and LADs in ESCs set the choice to associate with NL or nucleoli upon dissociation from their respective compartments during differentiation. The methodologies here developed will make possible to include the nucleolar contribution in nuclear space and genome function in diverse biological systems.

Role of Nuclear Lamina in Gene Repression and Maintenance of Chromosome Architecture in the Nucleus.

Nuclear lamina is a protein meshwork composed of lamins and lamin-associated proteins that lines the nuclear envelope from the inside and forms repressive transcription compartment. The review presents current data on the contribution of nuclear lamina to the repression of genes located in this compartment and on the mechanisms of chromatin attachment to the nuclear envelope.

Endothelial Nuclear Lamina in Mechanotransduction Under Shear Stress.

Endothelial cells that line the lumen of blood vessels are at the interface between hemodynamic forces and vascular wall biology. Endothelial cells transduce mechanical and biological signals from blood flow into intracellular signaling cascades through a process called mechanotransduction. Mechanotransduction is an important part of normal cell functions, as well as endothelial dysfunction which leads to inflammation and pathological conditions. For example, atherosclerosis preferentially develops in regions of disturbed fluid flow and low shear stress. The nuclear lamina, which sits underneath the nuclear envelope, serves to maintain the nuclear structure while acting as a scaffold for heterochromatin and many transcriptional proteins. Defects in lamina and its associated proteins cause a variety of human diseases including accelerated aging diseases such as Hutchinson-Gilford Progeria syndrome. The role of nuclear lamina in endothelial mechanotransduction, specifically how nuclear mechanics impact gene regulation under shear stress, is not fully understood. In one study, lamin A/C was silenced in bovine aortic endothelial cells to determine its role in both glucocorticoid receptor (GR) nuclear translocation and glucocorticoid response element (GRE) transcriptional activation in response to its natural ligand dexamethasone as well as fluid shear stress. Results suggest that absence of lamin A/C does not hinder passage of GR into the nucleus but nuclear lamina is important to properly regulate GRE transcription. Ongoing research continues to investigate how nuclear lamins contribute to endothelial mechanotransduction and to better understand the role of Lamin A in vascular aging and in the progression of cardiovascular diseases.