# Gene regulation for stem cell differentiation

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $376,950

## Abstract

ABSTRACT
 UTX is a chromatin modifier required for the development of brain, heart, and bone. To facilitate gene
activation, UTX removes methylation from methylated lysine 27 in histone H3 (H3K27 methylation) and
promotes H3K27 acetylation, H3K4 methylation, and open chromatin structure. In humans, UTX mutations are
causally linked to a developmental syndrome and to many childhood and adult cancers of the brain, blood,
bladder, esophagus, kidney, and breast. Although the importance of UTX is established, how it targets and
regulates genes remains unclear. In particular, contradictory findings raise the question about which chromatin
modifying activity of UTX is important for developmental gene regulation in stem cells. This knowledge gap
limits our understanding of the etiology of developmental defects and cancers associated with UTX dysfunction
or H3K27 modifications.
 Our long-term goal is to fill this knowledge gap by determining how UTX regulates chromatin structure
and gene expression to govern stem cell functions. Our preliminary studies identified a protein network of UTX
that is important for the differentiation of human pluripotent stem cells to the neural lineage. In this network,
DNA damage response factors play a noncanonical role in regulating gene expression. Our central hypothesis
is that this UTX-centric network facilitates chromatin changes and transcriptional activation during stem cell
differentiation. To test this hypothesis, we plan to identify the chromatin-regulatory activity of UTX that affects
transcription, examine the noncanonical function of DNA damage response factors in this network, and
elucidate the role of a downstream effector that executes gene expression programming. Our approaches will
take advantage of the conceptual innovation about a new UTX-driven protein network and the technological
innovation of combining Cas9-CRISPR for structure–function studies, genomics assays, and the human
cortical organoid model. If successful, we expect our findings to have wide implications on epigenetic
regulation of human stem cells in development and cancer.

## Key facts

- **NIH application ID:** 10001557
- **Project number:** 5R01GM134358-02
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Jamy C. Peng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $376,950
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001557

## Citation

> US National Institutes of Health, RePORTER application 10001557, Gene regulation for stem cell differentiation (5R01GM134358-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001557. Licensed CC0.

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