EHMT1是一种具有组蛋白甲基转移酶活性的表观遗传因子,在Kleefstra综合征中出现突变,一种以发育迟缓为特征的神经发育遗传疾病,智力残疾,和自闭症的特征。尽管该基因的功能和疾病的分子病因的研究最近取得了进展,我们对EHMT1单倍功能不全如何导致Kleefstra综合征的了解仍然非常有限.这里,我们发现RPE1细胞中EHMT1的耗竭导致不同亚细胞结构的形态和分布改变,比如高尔基体,溶酶体和不同的细胞粘附成分。EHMT1下调也增加了centriar卫星检测,这可能表明EHMT1在中心体功能中的作用。此外,EHMT1耗尽细胞的迁移过程也发生了改变,显示迁移能力降低。我们认为所描述的表型可以为理解Kleefstra综合征中EHMT1单倍体功能不全的功能影响开辟新的可能性。有助于阐明表观遗传调控与导致这种神经发育障碍的潜在细胞机制之间的联系。这些知识不仅与这种综合征的治疗有关,但也适用于其他神经发育条件,这些条件可能共享类似的失调的细胞途径。
EHMT1 is an epigenetic factor with histone methyltransferase activity that appears mutated in Kleefstra syndrome, 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 components.
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 neurodevelopmental 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.