Details

Autor(en) / Beteiligte

• Fujimura, Naoko
• Kuzelova, Andrea
• Ebert, Anja
• Strnad, Hynek
• Lachova, Jitka
• Machon, Ondrej
• Busslinger, Meinrad
• Kozmik, Zbynek

Titel

Polycomb repression complex 2 is required for the maintenance of retinal progenitor cells and balanced retinal differentiation

Ist Teil von

• Developmental biology, 2018-01, Vol.433 (1), p.47-60

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• Polycomb repressive complexes maintain transcriptional repression of genes encoding crucial developmental regulators through chromatin modification. Here we investigated the role of Polycomb repressive complex 2 (PRC2) in retinal development by inactivating its key components Eed and Ezh2. Conditional deletion of Ezh2 resulted in a partial loss of PRC2 function and accelerated differentiation of Müller glial cells. In contrast, inactivation of Eed led to the ablation of PRC2 function at early postnatal stage. Cell proliferation was reduced and retinal progenitor cells were significantly decreased in this mutant, which subsequently caused depletion of Müller glia, bipolar, and rod photoreceptor cells, primarily generated from postnatal retinal progenitor cells. Interestingly, the proportion of amacrine cells was dramatically increased at postnatal stages in the Eed-deficient retina. In accordance, multiple transcription factors controlling amacrine cell differentiation were upregulated. Furthermore, ChIP-seq analysis showed that these deregulated genes contained bivalent chromatin (H3K27me3+ H3K4me3+). Our results suggest that PRC2 is required for proliferation in order to maintain the retinal progenitor cells at postnatal stages and for retinal differentiation by controlling amacrine cell generation. [Display omitted] •Polycomb repressive complex 2 regulates proliferation in order to maintain the postnatal retinal progenitor cells.•Ezh2- and Eed-deficient retinae exhibit distinct aberrations in neuronal differentiation.•Amacrine-specific genes contain bivalent H3K4me3/H3K27me3 chromatin domains and are deregulated in the Eed-deficient retina.•The proportion of amacrine cells is increased in the Eed-deficient retina.