鉴定小鼠视网膜发育中的模块化超级增强子
Identification of a modular super-enhancer in murine retinal development.
机构信息
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Graduate School of Biomedical Sciences, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
出版信息
Nat Commun. 2022 Jan 11;13(1):253. doi: 10.1038/s41467-021-27924-y.
Super-enhancers are expansive regions of genomic DNA comprised of multiple putative enhancers that contribute to the dynamic gene expression patterns during development. This is particularly important in neurogenesis because many essential transcription factors have complex developmental stage- and cell-type specific expression patterns across the central nervous system. In the developing retina, Vsx2 is expressed in retinal progenitor cells and is maintained in differentiated bipolar neurons and Müller glia. A single super-enhancer controls this complex and dynamic pattern of expression. Here we show that deletion of one region disrupts retinal progenitor cell proliferation but does not affect cell fate specification. The deletion of another region has no effect on retinal progenitor cell proliferation but instead leads to a complete loss of bipolar neurons. This prototypical super-enhancer may serve as a model for dissecting the complex gene expression patterns for neurogenic transcription factors during development. Moreover, it provides a unique opportunity to alter expression of individual transcription factors in particular cell types at specific stages of development. This provides a deeper understanding of function that cannot be achieved with traditional knockout mouse approaches.
超级增强子是基因组 DNA 的扩展区域,由多个假定的增强子组成,这些增强子有助于在发育过程中形成动态的基因表达模式。这在神经发生中尤为重要,因为许多必需的转录因子在中枢神经系统中具有复杂的发育阶段和细胞类型特异性表达模式。在发育中的视网膜中,Vsx2 在视网膜祖细胞中表达,并在分化的双极神经元和 Müller 胶质细胞中维持。一个单一的超级增强子控制着这种复杂和动态的表达模式。在这里,我们表明,删除一个区域会破坏视网膜祖细胞的增殖,但不会影响细胞命运的指定。另一个区域的缺失对视网膜祖细胞的增殖没有影响,但会导致双极神经元的完全缺失。这个典型的超级增强子可以作为一个模型,用于在发育过程中解析神经发生转录因子的复杂基因表达模式。此外,它为在特定发育阶段的特定细胞类型中改变单个转录因子的表达提供了一个独特的机会。这提供了对功能的更深入理解,而传统的基因敲除小鼠方法无法实现这一点。