# Initial Characterization of WDR5B Reveals a Role in the Proliferation of Retinal Pigment Epithelial Cells

## TL;DR

This study explores WDR5B, a protein similar to WDR5, and finds it plays a role in the growth of retinal pigment epithelial cells.

## Contribution

The study is the first to characterize WDR5B and reveal its distinct role in cell proliferation compared to WDR5.

## Key findings

- WDR5B is upregulated during neural differentiation and has low expression in pluripotent cells.
- Knocking out WDR5B impairs the growth of retinal pigment epithelial cells.
- WDR5B shows minimal chromatin enrichment at sites where WDR5 is typically found.

## Abstract

The chromatin-associated protein WDR5 has been widely studied due to its role in histone modification and its potential as a pharmacological target for the treatment of cancer. In humans, the protein with highest sequence homology to WDR5 is encoded by the retrogene WDR5B, which remains unexplored. Here, we used CRISPR-Cas9 genome editing to generate WDR5B knockout and WDR5B-FLAG knock-in cell lines for further characterization. In contrast to WDR5, WDR5B exhibits low expression in pluripotent cells and is upregulated upon neural differentiation. Loss or shRNA depletion of WDR5B impairs cell growth and increases the fraction of non-viable cells in proliferating retinal pigment epithelial (RPE) cultures. CUT&RUN chromatin profiling in RPE and neural progenitors indicates minimal WDR5B enrichment at established WDR5 binding sites. These results suggest that WDR5 and WDR5B exhibit several divergent biological properties despite sharing a high degree of sequence homology.