Viny Lab

TL;DR Stag2 enforces erythroid fate by shaping chromatin to guide GATA1 binding, showing how TFs + chromatin = cell fate

We had so much fun working with Hongxia &🩸giant Mohan Narla. We appreciate funding support from NCI, @ash.hematology.org, @the-asci.bsky.social, #EvansMDS @damonrunyon.org

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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.

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Human Relevance
We extended findings to human CD34⁺ cells & MDS patients:
- STAG2 loss impaired erythroid differentiation
- Altered GATA1 target gene expression

🧍‍♂️➡️🧬⬅️🐭

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Functional Validation
Functionally, we observed that Stag2 KO EryPs:
- Produced fewer erythroid cells
- Generated more megakaryocytes

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Multi-omic Insight
RNA-seq, ATAC-seq, and GATA1 CUT&RUN of EryPs revealed:
- ↓ accessibility & GATA1 binding at erythroid genes
- ↑ accessibility & GATA1 binding at megakaryocyte genes

Stag2 loss rewires the GATA1 cistrome.

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Phenotypic Findings
Loss of Stag2 led to:
- ↓ erythroid progenitors
- ↑ megakaryocyte progenitors and megakaryocytes
Impaired terminal erythroid maturation

Basically, the hematopoietic GPS got rerouted.
🧭➡️🧬

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a man in a pirate costume is holding a camera and pointing ALT: a man in a pirate costume is holding a camera and pointing

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.

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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.

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Stag2 dependent chromatin remodeling enforces the erythroid-specific Gata1 cistrome The transcription factor GATA1 has pleiotropic hematopoietic functions, particularly in erythroid and megakaryocytic ontogeny. While mechanistic investigations have uncovered many facets of GATA1 biol...

🚨 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...

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Educational Session: “Dysregulation of nuclear topology in cancer: Clinical implications and emerging mechanisms”
Presenter:
@thedoctorisvin.bsky.social
April 25, 2025, 3:30 PM - 3:50 PM CST/ 4:30 PM - 4:50 PM EST

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If you’re at @theaacr.bsky.social don’t miss today’s session on 3D Topology & Cancer featuring giants of the field: Jane Skok @nyulangone.bsky.social & Brad Cairns @utah.edu

Imposter syndrome at an all time high! 😬

Proud to represent @cohesinlab.bsky.social @columbiacancer.bsky.social #AACR25

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