Chromatin dynamics governed by a set of nuclear structural proteins

Abstract

During the past three decades, the study of nuclear and chromatin organization has become of great interest. The organization and dynamics of chromatin are directly responsible for many functions including gene regulation, genome replication, and maintenance. In order to better understand the details of these mechanisms, we need to understand the role of specific proteins that take part in these processes. The genome in the nucleus is organized in different length scales, ranging from the bead‐like nucleosomes through topological associated domains up to chromosome territories. The mechanisms that maintain these structures, however, remain to be fully elucidated. Previous works highlighted the significance of lamin A, an important nucleoplasmic protein; however, there are other nuclear structural proteins that are also important for chromatin organization. Studying the organizational aspects of the nucleus is a complex task, and different methods have been developed and adopted for this purpose, including molecular and imaging methods. Here we describe the use of the live‐cell imaging method and demonstrate that the dynamics of the nucleus is strongly related to its organizational mechanisms. We labeled different genomic sites in the nucleus and measured the effect of nuclear structural proteins on their dynamics. We studied lamin A, BAF, Emerin, lamin B, CTCF, and Cohesin and discuss how each of them affect chromatin dynamics. Our findings indicate that lamin A and BAF have a significant effect on chromosomes dynamics, while other proteins mildly affect the type of the diffusion while the volume of motion is not affected.

Reorganization of the nuclear architecture in the Drosophila melanogaster Lamin B mutant lacking the CaaX box

“…Apparently, the CaaX box is not required for this interaction, since the majority of Lamin B was associated with polytene chromosomes in the Lam A25 salivary glands (Figures S5, S6). Other studies suggest that the ⍺-helical rod domain is necessary for the interaction of Lamin B with DNA or histones of the chromatin [3,16,40]. The ⍺-helical rod domain, which is intact in the Lam A25 mutant, may be responsible for colocalization of Lamin B with polytene chromosomes.…”

The Interchromatin Compartment Participates in the Structural and Functional Organization of the Cell Nucleus

“…Molecular studies and advanced imaging approaches, including live‐cell studies, have demonstrated that lamin A is responsible for the global long‐range stability of chromatin throughout the whole nuclear space, whereas other structural proteins, such as BAF, Emerin, lamin B, CTCF, and cohesion mildly affect the type of the diffusion, while the extent of motions is not affected . A‐type lamins or a protein complex containing lamin A may generate scaffolds expanding through the nuclear space that regulate many functions, including chromatin organization, gene transcription, DNA replication, DNA damage response, as well as cell cycle progression, cell differentiation, and cell migration . The scaffolding protein SAF‐A interacts with chromatin‐associated RNAs and forms a chromatin mesh in a transcription‐dependent manner .…”

The three‐dimensional cancer nucleus

“…Much more needs to be learned about the role that lamin A/C and other structural proteins play in cancer cells . A recent review by Sakthivel and Sehgal discusses potential roles of lamin A/C as a tumor biomarker, where increased expression is associated with aggressive colon cancer and higher Gleason scores in prostate cancer.…”

“…Lamin A/C are type V intermediate filament proteins that are required for the stability of the nuclear organization. 57,58 Cells from lamin A/C knock-out mice show an altered 3D telomere organization and an increase in genomic instability. 59 Such cells also display enhanced movement of telomeres.…”