| Autor: |
Honnell, Victoria, Sweeney, Shannon, Norrie, Jackie, Parks, Madison, Ramirez, Cody, Jannu, Asha Jacob, Beisi Xu, Teubner, Brett, Ah Young Lee, Bell, Claire, Dyer, Michael A. |
| Předmět: |
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| Zdroj: |
Development (09501991); Jul2024, Vol. 151 Issue 14, p1-12, 12p |
| Abstrakt: |
Super-enhancers (SEs) are expansive regions of genomic DNA that regulate the expression of genes involved in cell identity and cell fate. We recently identified developmental stage- and cell type-specific modules within the murine Vsx2 SE. Here, we show that the human VSX2 SE modules have similar developmental stage- and cell typespecific activity in reporter gene assays. By inserting the human sequence of one VSX2 SE module into a mouse with microphthalmia, eye sizewas rescued. To understand the function of these SEmodules during human retinal development, we deleted individual modules in human embryonic stemcells and generated retinal organoids. Deleting one module results in small organoids, recapitulating the small-eyed phenotype of mice with microphthalmia, while deletion of the other module led to disruptions in bipolar neuron development. This prototypical SE serves as a model for understanding developmental stage- and cell type-specific effects of neurogenic transcription factors with complex expression patterns. Moreover, by elucidating the gene regulatory mechanisms, we can begin to examine how dysregulation of these mechanisms contributes to phenotypic diversity and disease. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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