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Updated: Jun 22, 2025

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RUNX1 Isoforms Regulate RUNX1 and Target-Genes Differentially in Platelets-Megakaryocytes: Association with Clinical

Liying Guan1, Deepak Voora2, Rachel Myers3

  • 1Sol Sherry Thrombosis Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA.

Biorxiv : the Preprint Server for Biology
|July 1, 2024
PubMed
Summary

RUNX1 isoforms B and C differentially regulate gene expression and their own production. These isoforms are linked to cardiovascular disease acute events, with RUNX1C potentially offering protection.

Keywords:
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Area of Science:

  • Hematology
  • Molecular Biology
  • Genetics

Background:

  • Hematopoietic transcription factor RUNX1 (Runt-related transcription factor 1) exists as isoforms B and C, produced from distinct promoters.
  • The specific roles of RUNX1 isoforms in autoregulation and downstream gene control within megakaryocytes and platelets remain largely uncharacterized.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of RUNX1 isoforms B and C on RUNX1 gene expression and its target genes.
  • To investigate the association of RUNX1 isoforms and their target genes with acute events in cardiovascular disease (CVD).

Main Methods:

  • Studies involved megakaryocytic HEL cells, RUNX1-null HeLa cells, and platelets from healthy volunteers.
  • Chromatin immunoprecipitation, luciferase reporter assays, and RNA sequencing were employed.
  • Association analysis was performed between RUNX1 target genes and acute events in CVD patients.

Main Results:

  • RUNX1 isoforms B and C differentially bound and regulated RUNX1 promoters (P1 and P2).
  • Overexpression of RUNX1B and RUNX1C in HEL cells altered the expression of other RUNX1 isoforms and target genes (e.g., MYL9, F13A1).
  • RUNX1 isoform expression in platelets correlated with specific gene expression patterns, and certain RUNX1 targets were associated with acute CVD events.

Conclusions:

  • RUNX1 isoforms B and C exhibit distinct autoregulatory functions and differential control over downstream genes.
  • The observed differential regulation by RUNX1 isoforms is associated with acute events in cardiovascular disease patients.