Department of Biochemistry and Medical Genetics, University of Manitoba, 745 Bannatyne Avenue, Winnipeg MB R3E 0J9, Canada.
Ann Anat. 2010 Sep 20;192(5):261-74. doi: 10.1016/j.aanat.2010.07.009. Epub 2010 Aug 6.
The process of mammalian development is established through multiple complex molecular pathways acting in harmony at the genomic, proteomic, and epigenomic levels. The outcome is profoundly influenced by the role of epigenetics through transcriptional regulation of key developmental genes. Epigenetics refer to changes in gene expression that are inherited through mechanisms other than the underlying DNA sequence, which control cellular morphology and identity. It is currently well accepted that epigenetics play central roles in regulating mammalian development and cellular differentiation by dictating cell fate decisions via regulation of specific genes. Among these genes are the Hox family members, which are master regulators of embryonic development and stem cell differentiation and their mis-regulation leads to human disease and cancer. The Hox gene discovery led to the establishment of a fundamental role for basic genetics in development. Hox genes encode for highly conserved transcription factors from flies to humans that organize the anterior-posterior body axis during embryogenesis. Hox gene expression during development is tightly regulated in a spatiotemporal manner, partly by chromatin structure and epigenetic modifications. Here, we review the impact of different epigenetic mechanisms in development and stem cell differentiation with a clear focus on the regulation of Hox genes.
哺乳动物的发育过程是通过多个复杂的分子途径在基因组、蛋白质组和表观基因组水平上协同作用建立的。表观遗传学通过关键发育基因的转录调控，对发育的结果有着深远的影响。表观遗传学是指基因表达的变化，这些变化是通过除基础 DNA 序列以外的机制遗传的，这些机制控制着细胞的形态和身份。目前人们普遍认为，表观遗传学通过调节特定基因，决定细胞命运的决定，在调节哺乳动物发育和细胞分化方面发挥着核心作用。这些基因包括 Hox 家族成员，它们是胚胎发育和干细胞分化的主要调控因子，其失调会导致人类疾病和癌症。Hox 基因的发现确立了基础遗传学在发育中的基本作用。Hox 基因编码的转录因子在从苍蝇到人类的生物中高度保守，在胚胎发生过程中组织身体前后轴。Hox 基因在发育过程中的表达受到时空的严格调控，部分是由染色质结构和表观遗传修饰调控的。在这里，我们综述了不同的表观遗传机制在发育和干细胞分化中的作用，重点关注 Hox 基因的调控。
