Chromatin compartments define distinct modes of action and biological roles of the pioneer Pax7
Pioneer transcription factors direct cell differentiation by remodeling closed chromatin to deploy new enhancers. It remains unclear how the chromatin context shapes their action. During pituitary development, the pioneer PAX7 opens thousands of enhancers and specifies the melanotrope cell fate. We report that PAX7 acts in both the A (active) and B (inactive) genomic compartments, engaging two…
Pioneer transcription factors shape cell differentiation through the remodeling of chromatin, making way for new enhancers. However, the impact of chromatin context on their action remains unclear. During pituitary development, the pioneer factor PAX7 opens thousands of enhancers, leading to the specification of the melanotrope cell fate. This study reveals that PAX7 operates in both active (A) and inactive (B) genomic compartments, engaging two unique closed states.
In the A compartment, enhancers open in a single, cell-division-independent step within a H1-enriched chromatin environment. Conversely, the B compartment opening demands cell division, resulting in the dissociation of lamin proteins and a shift from the B to the A compartment. These two modes of action yield different biological outputs: the A compartment modulates genes expressed broadly across the cell, while the B compartment drives the de novo expression of cell-type-specific developmental genes essential for melanotrope identity.
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