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YY1 protein is essential for the promotion of Muller glia reprogramming and retina regeneration

Chaudhary, M.; Desai, O. M.; Sharma, P.; Premraj, S.; Shukla, P.; Ramachandran, R.

2025-02-03 cell biology
10.1101/2025.01.31.635905 bioRxiv
Show abstract

Unlike mammals, the Muller glia reprogramming in zebrafish retina restores vision after an acute retinal injury. Here, we explored the Ying yang (Yy1) protein and its multi-faceted roles in different phases of retina regeneration. We show that the acetylation and deacetylation status of Yy1 contribute to its transcriptional activation and repression functions on various target genes, including regeneration-associated genes (RAGs). Yy1 is regulated positively by TGF-{beta} and negatively through Delta-Notch signaling in the injured retina. Yy1-knockdown caused reduced retinal progenitor induction and regeneration, while the opposite was seen in its overexpression. Yy1 collaborates with histone deacetylases, BAF complex, and the effector of TGF-{beta} signaling, pSMAD3, to target the genome differentially. Lastly, the whole transcriptome analysis of the Yy1-debilitated retina revealed differential expression of various RAGs and BMP-signaling. Yy1 facilitates the BMP pathways genes through the downregulation of noggin3. Our study unravels how a single transcription factor, Yy1, could influence many important regulatory steps of retina regeneration.

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