Summary We identify Stag2 as a key enforcer of erythroid identity through its role in shaping the chromatin landscape that guides Gata1 binding. This underscores the importance of coordinated transcription factor and chromatin interactions in lineage specification.
Human Relevance We extended findings to human CD34⁺ cells & MDS patients: - STAG2 loss impaired erythroid differentiation - Altered GATA1 target gene expression
Phenotypic Findings Loss of Stag2 led to: - ↓ erythroid progenitors - ↑ megakaryocyte progenitors and megakaryocytes Impaired terminal erythroid maturation
Basically, the hematopoietic GPS got rerouted. 🧭➡️🧬
Hypothesis and Model We hypothesized that Stag2, a cohesin complex member recurrently mutated in MDS, modulates chromatin accessibility to guide GATA1’s lineage-specific binding. To test this, we profiled erythropoiesis in Stag2 KO mice.
GATA1 is a master regulator of 🩸, yet it has pleiotropic functions, particularly in erythroid/megakaryocytic ontogeny. Inspired by the open Qs in John Crispino's review (PMID: 15659348) we wanted to understand how GATA1 enforces lineage specificity across divergent fates.
🚨 Excited to share our new preprint: Stag2 dependent chromatin remodeling enforces the erythroid-specific Gata1 cistrome. This work was led by Columbia VP&S MD student Varun Sudunagunta (‼️ Program Directors: Varun is applying to IM residencies this year!) www.biorxiv.org/content/10.1...
