Retinal development requires the timely and coordinated generation of neural and glial cell types from retinal progenitor cells (RPCs). This process is regulated by DNA methylation through the activity of various proteins, including the DNA-binding protein UHRF1. Now, Timothy Hallstrom and colleagues identify a new role for UHRF2, a paralog of UHRF1, in controlling the differentiation of mouse retinal progenitors. They find that Uhrf2 deletion causes excess proliferation and thus retinal hypercellularity during postnatal development, potentially resulting from changes in the expression and post-translational modification of cell cycle regulators. Moreover, loss of UHRF2 leads to a reduction in RPCs and delays the production of cone cells, whereas retinal ganglion cells are overproduced. The development of late cells, namely rods, bipolar cells, horizontal cells and Müller glia, is also delayed in Uhrf2-knockout mice. The authors further show that the levels of 5-hydroxymethylcytosine (5hmC), a DNA modification regulating cellular differentiation, are reduced during retinal development upon Uhrf2 deletion. Specifically, 5hmC in the gene body of genes within the active demethylation pathway, which produces 5hmC, are decreased. This coincides with their lower expression and could contribute to the overall loss of 5hmC in retinal progenitors. Collectively, these findings establish UHRF2 as a novel epigenetic regulator of gene expression and the cell cycle in retinal development.
Ensuring timely differentiation during retinal development
Ensuring timely differentiation during retinal development. Development 15 March 2022; 149 (6): e149_e0601. doi:
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