# Function of MLL in transcription regulation

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $350,854

## Abstract

Project Summary
Cell identity is determined by cell specific transcription circuitry that integrate information of cell
history and extracellular cues. It often involves multilayered regulation at the level of chromatin.
Epigenomic studies have identified conserved chromatin features associated with transcription
activation. Among them is enrichment of histone H3 K4 methylation at cis-regulatory elements
including gene promoters and enhancers. These regulatory sequences often function as
integrated transcription factor binding platforms that have unexpected complexity and dynamics
in different cell types. In mammal, H3 K4 methylation is deposited by the mixed lineage
leukemia (MLL) family of enzymes. Each MLL plays an essential and non-redundant function
during embryonic development. Recurrent mutations in MLLs are reported in many human
diseases including developmental disorders, cancers and immunological diseases. However,
questions of specific function and regulation of each MLL remain. It is also unclear whether the
enzymatic activity of MLLs has any obligatory role in transcription regulation. Here we will
examine the function of MLL1, the founding member of the MLL family, in cell fate determination
and transition using a robust stem cell differentiation and reprograming model. We will dissect
the essential function of each MLL1 domain including the catalytic SET domain in cell fate
determination. We will also examine the mechanism by which MLL1 regulates transcription and
how it may be distinct from other MLLs. Our study will provide novel insights into basic
mechanisms of pluripotency and gene regulation.

## Key facts

- **NIH application ID:** 10212397
- **Project number:** 5R01GM082856-11
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Yali Dou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $350,854
- **Award type:** 5
- **Project period:** 2009-04-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212397

## Citation

> US National Institutes of Health, RePORTER application 10212397, Function of MLL in transcription regulation (5R01GM082856-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10212397. Licensed CC0.

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