The Emerging Roles of Heterochromatin in Cell Migration

Abstract

Cell migration is a key process in health and disease. In the last decade an increasing attention is given to chromatin organization in migrating cells. In various types of cells induction of migration leads to a global increase in heterochromatin levels. Heterochromatin is required for optimal cell migration capabilities, since various interventions with heterochromatin formation impeded the migration rate of numerous cell types. Heterochromatin supports the migration process by affecting both the mechanical properties of the nucleus as well as the genetic processes taking place within it. Increased heterochromatin levels elevate nuclear rigidity in a manner that allows faster cell migration in 3D environments. Condensed chromatin and a more rigid nucleus may increase nuclear durability to shear stress and prevent DNA damage during the migration process. In addition, heterochromatin reorganization in migrating cells is important for induction of migration-specific transcriptional plan together with inhibition of many other unnecessary transcriptional changes. Thus, chromatin organization appears to have a key role in the cellular migration process.

HP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics

“…It remains unclear whether HP1α's phase separation capability is important to this biophysical function. More broadly, our experiments demonstrate that mechanical softening of the nucleus due to loss of HP1α's chromatin crosslinking ability, rather than transcriptional changes, could underlie defects in fundamental nuclear functions such as nuclear compartmentalization, DNA damage prevention and response, and migration, all of which have been shown to depend on nuclear mechanics (Gerlitz, 2020;Stephens, 2020;Xie et al, 2020). These mechanical changes could also have broad implications for human diseases, such as breast cancer, where increased invasiveness (migration ability) has been correlated with decreased HP1α levels (Vad- Nielsen and Nielsen, 2015) and inhibition of HP1α dimerization (Norwood et al, 2006).…”

Chitosan Micro-Grooved Membranes with Increased Asymmetry for the Improvement of the Schwann Cell Response in Nerve Regeneration

“…Again, the SCA pattern’s asymmetry is reflected in the nuclear morphology, thus leaving a greater freedom for the nuclear shaping, such as for cells. The nuclear shaping also impacts the gene expression and epigenetic markers [ 43 ], likely further contributing to the cell behavior on the different topographies.…”

SETDB1 regulates microtubule dynamics

“…Taken together, it seems that SETDB1 can affect various aspects of tumor progression such as cell division and cell migration, at multiple levels by different mechanisms. At the chromatin level, it can affect transcriptional control of key factors to support cell migration and proliferation (Gerlitz, 2020; Orouji et al, 2019; Yu et al, 2019) and it can promote global chromatin condensation to support cell migration (Gerlitz, 2020; Maizels et al, 2017); while at the MT level, it can modulate MT dynamics probably by affecting the activity and/or the binding of MAPs to MTs. Indeed, we were able to identify interaction between SETDB1 and the tubulin deacetylase HDAC6, as well as increased tubulin acetylation levels following SETDB1 KD.…”

“…The second is that acetylation of Lys40 in -tubulin (acetylated tubulin) is a key tubulin posttranslational modification, which is associated with stable MTs in various cellular contexts (A et al, 2020;Li and Yang, 2015). We hypothesized that SETDB1 may interact with a tubulin HDAC and affect its activity.…”