9/1/2023 0 Comments Chromosome scaffold proteinHowever, our knowledge of the precise relationship between composition of NuMat and MiCS remains limited. This arrangement of DNA loops in mitotic chromosomes is similar to the DNA loops that are attached to NuMat in interphase nucleus ( 14, 15).Ĭonsidering that NuMat and mitotic chromosome scaffold (MiCS) are comparable biochemical structures, it is reasonable to expect that at least certain components of the NuMat are retained in MiCS ( 16, 17). Early evidence for transmission of information for higher order chromatin organization through mitosis came from the pioneering work by Laemmli and co-workers, who showed that in histone depleted mitotic chromosomes, DNA loops are attached to a proteinaceous scaffold. For example, chromosome positions are transmitted through mitosis and non-random higher order chromatin arrangements can be stably propagated over many cell cycles ( 12, 13). Several studies suggest that along with this, the information for 3D organization of chromatin in the nucleus is also stably inherited in daughter cells. One of the mechanisms by which this is accomplished is by bookmarking of genes mediated by locus specific retention of transcription factors and deposition of heritable epigenetic marks ( 9 – 11). Most genes are thought to be silenced during cell division but are precisely re-activated in daughter cells to achieve gene expression pattern that is indistinguishable from the mother cell ( 7, 8). However, during open mitosis the three-dimensional organization of the nucleus breaks down as the chromosomes condense to enable faithful segregation of duplicated chromatids into daughter cells. NuMat, along with facilitating the packaging of DNA, organizes the nuclear microenvironment in a way that transcription, replication, splicing and repair are executed in a coordinated manner over the highly compacted DNA. Specific attachment of chromatin fibers to NuMat create a higher order structure made up of discrete topological loop domains ( 5, 6). During interphase, interior of the nucleus is organized on a ribonucleo-protein network known as nuclear matrix (NuMat) 1 ( 4). Genetic information that is encoded in a linear DNA sequence, needs to be organized in three-dimensional space of the nucleus in the form of chromatin for appropriate expression of genes ( 1 – 3). Our study clearly indicates that the features of nuclear architecture, in the structural context of NuMat, are retained in MiCS and possibly play an important role in maintenance of cell lineage specific transcriptional status during cell division and thereby, serve as components of cellular memory. Although several transcription factors involved in functioning of interphase nucleus are present exclusively in NuMat, protein components responsible for assembly of membrane-less nuclear bodies are uniquely retained in MiCS. Chromatin/RNA binding proteins with hydrolase and helicase activity are highly enriched in NuMat as well as MiCS. ![]() Proteins of the NuMat/MiCS have large dynamic range of MS signal and were detected in sub-femtomolar amounts. ![]() Our study elucidates that as much as 67% of the NuMat proteins are retained in the MiCS indicating that the features of nuclear architecture in interphase nucleus are retained on the mitotic chromosomes. ![]() We compared the proteome of nuclease and high salt resistant fraction of interphase nucleus known as nuclear matrix (NuMat) and an equivalent biochemical fraction in the mitotic chromosome known as mitotic chromosome scaffold (MiCS). This necessitates that the features of nuclear architecture and DNA topology persist through mitosis. Chromatin condenses several folds to form mitotic chromosomes during cell division and decondenses post-mitotically to reoccupy their nuclear territory and regain their specific transcriptional profile in a precisely lineage specific manner.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |