With this, I welcome questions, discussions, and suggestions!

8/8 Immense gratitude to my mentors and colleagues who made this work possible!

7/8 Together with our earlier Δ1+2+3 mice (lacking three CEBP sites in the same Zeb2 -165 kb enhancer, eliminated monocytes & cDC2s), this establishes that one pleiotropic enhancer can integrate:
• Pleiotropic sites (E-boxes: lymphoid and myeloid)
• Lineage-specific sites (CEBP sites: myeloid only)

6/8 This work has broader implications for enhancer biology. Unlike traditional enhancer switching or pleiotropic enhancers driven by shared pleiotropic TF motifs, I show that a single pleiotropic enhancer can be activated by distinct TFs in different cell types.

5/8 In the same double mutants, B cells were partially restored and pDCs were fully rescued, suggesting that ZEB2 supports these lineages by repressing Id2.

4/8 I regenerated Id2 deficient mice which completely lack cDC1s. Strikingly, double mutant mice lacking both Id2 and the Zeb2 -165-kb enhancer fully restored cDC1s, suggesting that ID2 secures cDC1 specification by neutralizing E protein activity at the Zeb2 enhancer.

3/8 Phenotypes of ΔE mice:
• Complete loss of B cells and pDCs
• Impaired NK cell maturation
• Increased ILC1s and ILC2s
• Increased cDC1 specification and compromised cDC2 development

2/8 I generated ΔE mice lacking three E-boxes within the Zeb2 -165-kb enhancer. These sites proved essential for Zeb2 expression in the lymphoid compartment and partly contributed to its activity in the myeloid compartment.