Despite their pivotal role in genome organization and its relevance to human disease, there are a great many aspects of lamin function in genome organization and regulation that require further investigation. Post-translational modifications of nuclear lamins, such as phosphorylation, not only regulate their assembly into the nuclear lamina, but can also regulate intra-nuclear lamin localization and sequestration of lamin interacting protein complexes.
However, the ability of lamin post-translational modifications to regulate chromatin interactions with the nuclear envelope in genome organization or associations with different complexes for intranuclear lamins has not been investigated. Furthermore, though phosphorylation has been the most investigated lamin post-translational modification, there is likely more glycosylation and sumoylation on lamins along with other modifications that are still being discovered.
Distinction of the roles of individual lamin isoforms - lamins A, A?10, progerin, B1, B2, B3, C, C2, and C3 have also been little investigated both with respect to genome organization and to the different protein complexes associating that also contribute genome regulation. The interaction of chromatin with lamins in Lamina Associated Domains (LADs) is generally associated with gene repression, but it is unclear to what extent this repression relates to lamins also being able to bind epigenetic modifier complexes to add silencing marks at LADs or the contribution of a steric or competition for binding function due to gene occupancy on LADs.
Topologically Associating Domains (TADs) tend to have boundaries from chromatin organizers such as CTCF and cohesins, but it is unclear to what degree the stoichiometry of A and B-type lamins that changes in a cell-type specific manner and its crosstalk with these chromatin organizers finetunes this chromatin compartmentalization and consequently transcriptional activity for different cell types. It is also unclear whether LADs themselves can act similarly to these chromatin organizers, supplanting their function.
It is beyond any doubt that cross disciplinary approaches of molecular, biophysical, cell biological, omics, imaging and computational analyses of lamins is essential in order to unravel the molecular underpinnings deregulated in envelopathies and diseases of the nucleus such as cancers and all such reports are welcome for this topic.
Despite their pivotal role in genome organization and its relevance to human disease, there are a great many aspects of lamin function in genome organization and regulation that require further investigation. Post-translational modifications of nuclear lamins, such as phosphorylation, not only regulate their assembly into the nuclear lamina, but can also regulate intra-nuclear lamin localization and sequestration of lamin interacting protein complexes.
However, the ability of lamin post-translational modifications to regulate chromatin interactions with the nuclear envelope in genome organization or associations with different complexes for intranuclear lamins has not been investigated. Furthermore, though phosphorylation has been the most investigated lamin post-translational modification, there is likely more glycosylation and sumoylation on lamins along with other modifications that are still being discovered.
Distinction of the roles of individual lamin isoforms - lamins A, A?10, progerin, B1, B2, B3, C, C2, and C3 have also been little investigated both with respect to genome organization and to the different protein complexes associating that also contribute genome regulation. The interaction of chromatin with lamins in Lamina Associated Domains (LADs) is generally associated with gene repression, but it is unclear to what extent this repression relates to lamins also being able to bind epigenetic modifier complexes to add silencing marks at LADs or the contribution of a steric or competition for binding function due to gene occupancy on LADs.
Topologically Associating Domains (TADs) tend to have boundaries from chromatin organizers such as CTCF and cohesins, but it is unclear to what degree the stoichiometry of A and B-type lamins that changes in a cell-type specific manner and its crosstalk with these chromatin organizers finetunes this chromatin compartmentalization and consequently transcriptional activity for different cell types. It is also unclear whether LADs themselves can act similarly to these chromatin organizers, supplanting their function.
It is beyond any doubt that cross disciplinary approaches of molecular, biophysical, cell biological, omics, imaging and computational analyses of lamins is essential in order to unravel the molecular underpinnings deregulated in envelopathies and diseases of the nucleus such as cancers and all such reports are welcome for this topic.
