It was extremely challenging to identify transcription factor binding profiles using mouse pre-implantation embryos due to the limited availability of material. I was fortunate to establish an optimised CUT&Tag protocol for this purpose in 2020.

Thank you very much!

Thank you, Johanna! See you at the conference!

Combining expertise with low-input genomics, biochemistry, and cryo-EM analysis, my group cross the scale to understand this fundamental question.

Dundee is a surprisingly sunny spot in Scotland, and I’m looking forward to enjoying life in the UK, surrounded by its beautiful nature!

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

Thank you, Ana!

Finally, this work is a great collaboration within the Tachibana lab!
🎉 Huge thanks to:
Chad for all bioinformatic analysis. Eda (a talented student!) helped CUT&Tag and biochemistry. Adarsh helped testing KD. (11/n)

This work represents technical culmination in my postdoc, combining embryology, genomics, biochemistry, and cryo-EM. Huge thanks to Kikuë and the fantastic core facilities at @MPI_Biochem ! (10/n)

Taken togther, NR5A2 regulates the expression of KLF5 and GATA6, which in turn function as NR5A2 co-regulators to ensures robust gene activation through feed-forward loops. (9/n)

Biochemical data further revealed that NR5A2 co-binds to nucleosomes with KLF5 and GATA6 in vitro, providing strong support that these pioneer factors simultaneously engage with chromatin to drive transcriptional activation in vivo. (8/n)

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 www.nature.com/articles/s41... (7/n)

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)

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)

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)

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)

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)
www.nature.com/articles/s41...