# RUNX1 Transcription and R-loop Formation in Hematopoiesis

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $38,917

## Abstract

Project Summary/Abstract
 Hematopoiesis, the process by which all blood cells are formed, is a complex and precisely regulated
program. Differentiation and maturation of hematopoietic stem cells (HSCs) is controlled by several key
factors, when perturbed hematopoiesis becomes dysregulated and leads to hematopoietic disorders and
related malignancies. A master regulator of hematopoiesis, RUNX1, is a DNA binding transcriptional factor
and contributes to HSC proliferation as well as differentiation. RUNX1 has been shown to control a broad, yet
poorly defined transcriptional program, binding to other key hematopoietic factors such as PU.1 and working
in cooperation with additional transcriptional regulators. Through protein-protein interaction studies, RUNX1
has been shown to bind co-activators such as p300 as well as co-repressors such as Sin3a. These discoveries
add an additional later of complexity to RUNX1 transcription while DNA binding motif studies have yielded a
core motif insufficient to describe RUNX1 binding. Currently, RUNX1 transcriptional mechanisms remain
poorly understood with only isolated reports of RUNX1 targets in hematopoiesis. Recent have demonstrated
that transcription factors regulate transcription through several mechanism beyond canonical DNA binding.
Promoter-enhancer interactions in addition to contributions to DNA looping allow transcription factors to
shape the 3D nucleome. In addition to RUNX1’s reported interaction with transcriptional regulators and new
studies show control of hematopoietic enhancers such as Myb are mediated by RUNX1. Despite its critical role
in hematopoiesis, the molecular mechanisms mediating RUNX1 transcription remain to be elucidated.
Furthermore, RUNX1 has been linked to R-loop formation, RNA:DNA hybrids formed during transcription
and linked to DNA damage. This places RUNX1 in a unique position, regulating transcription on a broad scale
through both DNA binding and DNA looping while also contributing to underlying DNA damage related
transcriptional processes. The proposal aims uncover the molecular mechanisms underlying RUNX1
transcriptional programs and greater role in R-loop formation. Utilizing new technologies to study promoter-
enhancer connections, RNA:DNA interactions and transcriptional hubs mediated by RUNX1 this project will
globally identify key RUNX1 targets regulating hematopoiesis. Additionally, the analysis of RUNX1 mediated
R-loop formation will uncover RUNX1’s role in transcription/replication stress and contribution to DNA
damage repair, demonstrated to constitute a key function in hematopoietic stem cell self-renewal and function.

## Key facts

- **NIH application ID:** 10364601
- **Project number:** 5F31HL152652-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Nathan Daniel Jayne
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,917
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364601

## Citation

> US National Institutes of Health, RePORTER application 10364601, RUNX1 Transcription and R-loop Formation in Hematopoiesis (5F31HL152652-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10364601. Licensed CC0.

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