Authors
Mensah, I. K., He, M., Zahoor, M., Khan, S. U., Emerson, M. L., Tan, H. J., Bolden, G. D., Utturkar, S. M., Gowher, H.
Abstract
Vascular Endothelial Zinc Finger 1 (VEZF1) is essential for embryonic development, but its role in pluripotency exit remains unclear. Previous work showed that Vezf1-deficient ESCs exhibit impaired differentiation, reduced Dnmt3b expression, and genome-wide hypomethylation. Here, we show that Vezf1-/- ESCs fail to efficiently repress the pluripotency transcriptional program during differentiation, a defect that persists after ectopic Dnmt3b expression. Genome-wide analysis revealed VEZF1 occupancy at regulatory regions of genes involved in several developmental signaling pathways, including MAPK, WNT, and Hippo, as well as at some pluripotency-associated genes. Many VEZF1-bound MAPK genes showed reduced expression in undifferentiated Vezf1-/- ESCs, suggesting that VEZF1 activity contributes to transcriptional competence required for efficient pluripotency exit. VEZF1 loss also led to widespread acquisition of new CTCF sites associated with developmental signaling, a subset of which overlapped VEZF1-bound regulatory regions. CTCF depletion had only limited effects on the expression of the VEZF1-bound MAPK genes examined, indicating that increased CTCF occupancy alone is insufficient to explain their reduced expression in Vezf1-/- ESCs. Together, our findings identify a DNMT3B-independent function of VEZF1 in facilitating the exit from pluripotency and establishing transcriptional competence for differentiation, while revealing a potential role for VEZF1 in regulating CTCF occupancy during developmental state transitions.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 19 Aug 2026.
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