Cell consequences of loss of function of the epigenetic factor EHMT1

EHMT1 is an epigenetic factor with histone methyltransferase activity that appears mutated in Kleefstra syn-drome, a neurodevelopmental genetic disorder characterized by developmental delay, intellectual disability, and autistic-like features. Despite recent progress in the study of the function of this gene and the molecular etiology of the disease, our knowledge of how EHMT1 haploinsufficiency causes Kleefstra syndrome is still very limited. Here, we show that EHMT1 depletion in RPE1 cells leads to alterations in the morphology and distribution of different subcellular structures, such as the Golgi apparatus, the lysosomes and different cell adhesion compo-nents. EHMT1 downregulation also increases centriolar satellites detection, which may indicate a role for EHMT1 in centrosome functioning. Furthermore, the migration process is also altered in EHMT1 depleted cells, which show reduced migration capacity. We consider that the described phenotypes could open new possibilities for understanding the functional impact of EHMT1 haploinsufficiency in Kleefstra syndrome, helping to elucidate the link between epigenetic regulation and the underlying cellular mechanisms that result in this neuro-developmental disorder. This knowledge could be relevant not only for the treatment of this syndrome, but also for other neurodevelopmental conditions that could share similar deregulated cellular pathways.

Automated summary

EHMT1 deficiency in cells leads to altered cellular structures and reduced migration capacity, indicating a functional impact on Kleefstra syndrome. The study suggests a potential link between EHMT1 haploinsufficiency, epigenetic regulation, and the cellular mechanisms underlying neurodevelopmental disorders.