🚀Excited to share preprint as my last work in the Tachibana lab! Our study shows how the pioneer factor NR5A2 ensures robust gene activation through feed-forward regulatory loops with lineage-determining factors. A quick summary follows (1/n) www.biorxiv.org/content/10.1... - ThreadSky

wkobayashi.bsky.social • 38 days ago

🚀Excited to share preprint as my last work in the Tachibana lab! Our study shows how the pioneer factor NR5A2 ensures robust gene activation through feed-forward regulatory loops with lineage-determining factors. A quick summary follows (1/n)
https://www.biorxiv.org/content/10.1101/2025.02.14.638292v1

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anajaneva.bsky.social•38 days ago

Congratulations Wataru!!

wkobayashi.bsky.social•38 days ago

Thank you, Ana!

wkobayashi.bsky.social•38 days ago

NR5A2 is a pioneer transcription factor essential for pre-implantation development in mice. We recently reported that NR5A2 facilitates gene expression by unwrapping nucleosomal DNA through minor groove anchor competition. (2/n)
https://www.nature.com/articles/s41594-024-01239-0

wkobayashi.bsky.social•38 days ago

We previously found that NR5A2 targets cell-type specific (putative) enhancers between 2-cell embryos (totipotency) and ESCs (pluripotency). We hypothesized that NR5A2 may cooperate with other TFs to control distinct transcriptional networks during totipotency-to-pluripotency transition. (3/n)

wkobayashi.bsky.social•38 days ago

We determined NR5A2 chromatin binding profiles from 2-cell to morula stage and identified KLF and GATA families as potential NR5A2 co-regulators. Klf5 and Gata6 were highly expressed in later developmental stages with their expression partially regulated by NR5A2. (4/n)

wkobayashi.bsky.social•38 days ago

Thus, NR5A2 acts upstream of these factors. Interestingly, these three TFs co-occupancy correlated with the gain of H3K27ac levels at the morula stage. We then addressed how NR5A2 functions together with KLF5 or GATA6. (5/n)

wkobayashi.bsky.social•38 days ago

Perturbation of both Nr5a2 and Klf5 caused severe developmental defects compared to that of Nr5a2 alone, highlighting synergistic roles of NR5A2 and KLF5. Mechanistically, NR5A2 promotes chromatin accessibility and facilitates H3K27ac deposition in cooperation with KLF5. (6/n)

wkobayashi.bsky.social•38 days ago

Surprisingly, Xist was down-regulated upon Nr5a2 KD. We found that NR5A2 regulates Gata1 and Gata6 expression and further binds Xist enhancers with GATA6, indicating that NR5A2 directly or indirectly regulates X-chromosome inactivation. Please also see https://www.nature.com/articles/s41556-023-01266-x (7/n)

joadelas.bsky.social•38 days ago

Looking forward to reading this new chapter! Congrats!

wkobayashi.bsky.social•38 days ago

Thank you very much. I moved to UK yesterday. It’s gonna be slow starting.

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