Ezeonwuka Chinelo D, Rastegar Mojgan
Regenerative Medicine Program, Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, Manitoba, R3E 0J9, Canada.
Diseases. 2014 Jan 27;2(1):45-70. doi: 10.3390/diseases2010045.
The role of epigenetics in human disease has become an area of increased research interest. Collaborative efforts from scientists and clinicians have led to a better understanding of the molecular mechanisms by which epigenetic regulation is involved in the pathogenesis of many human diseases. Several neurological and non-neurological disorders are associated with mutations in genes that encode for epigenetic factors. One of the most studied proteins that impacts human disease and is associated with deregulation of epigenetic processes is Methyl CpG binding protein 2 (MeCP2). MeCP2 is an epigenetic regulator that modulates gene expression by translating epigenetic DNA methylation marks into appropriate cellular responses. In order to highlight the importance of epigenetics to development and disease, we will discuss how MeCP2 emerges as a key epigenetic player in human neurodevelopmental, neurological, and non-neurological disorders. We will review our current knowledge on MeCP2-related diseases, including Rett Syndrome, Angelman Syndrome, Fetal Alcohol Spectrum Disorder, Hirschsprung disease, and Cancer. Additionally, we will briefly discuss about the existing MeCP2 animal models that have been generated for a better understanding of how MeCP2 impacts certain human diseases.
表观遗传学在人类疾病中的作用已成为一个研究兴趣日益浓厚的领域。科学家和临床医生的共同努力使人们对表观遗传调控参与多种人类疾病发病机制的分子机制有了更深入的了解。几种神经和非神经疾病与编码表观遗传因子的基因突变有关。甲基化CpG结合蛋白2(MeCP2)是研究最多的影响人类疾病且与表观遗传过程失调相关的蛋白质之一。MeCP2是一种表观遗传调节因子,通过将表观遗传DNA甲基化标记转化为适当的细胞反应来调节基因表达。为了突出表观遗传学对发育和疾病的重要性,我们将讨论MeCP2如何成为人类神经发育、神经和非神经疾病中关键的表观遗传参与者。我们将回顾我们目前对与MeCP2相关疾病的认识,包括雷特综合征、天使综合征、胎儿酒精谱系障碍、先天性巨结肠病和癌症。此外,我们将简要讨论为更好地理解MeCP2如何影响某些人类疾病而建立的现有MeCP2动物模型。