# Structural insights into the MLL core complexes

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $599,221

## Abstract

Project Summary
Cancer epigenetics is an emerging field of high significance. It has led to the identification of novel
therapeutic targets and biomarkers. Among chromatin remodeling complexes, driver mutations of the
MLL family histone methyltransferases are commonly found in cancer. They lead to epigenetic
aberrations that underlie cancer initiation, evolution, and metastasis. Understanding how the activity of
the MLL family enzymes on chromatin is regulated and how its dysregulation leads to malignancy will
shed light on disease mechanisms. We previously reconstituted a functionally active MLL1 core
complex in vitro and identified four MLL1 core complex components, i.e. ASH2L, RbBP5, WDR5 and
DPY30, which are essential for MLL1 enzymatic activity. Here we show that a novel function of ASH2L
in MLL1 regulation and a previously uncharacterized mode of action. We will use biochemical,
structural and epigenomic approaches to delineate how ASH2L confers new complexity to regulation of
H3K4 methylation and gene expression. We expect to establish a new paradigm on how epigenetic
heterogeneity is established by a well-defined MLL1 core complex, which also has general implications
for other chromatin modifying enzymes. Our study will ultimately benefit discovery of novel therapeutic
targets or biomarkers for cancer diagnosis and treatment. This project matches the mission of National
Cancer Institute (NCI).

## Key facts

- **NIH application ID:** 10246904
- **Project number:** 5R01CA250329-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Uhn-Soo Cho
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $599,221
- **Award type:** 5
- **Project period:** 2020-08-25 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246904

## Citation

> US National Institutes of Health, RePORTER application 10246904, Structural insights into the MLL core complexes (5R01CA250329-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246904. Licensed CC0.

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