# The Role of the Lysine-Specific Histone Demethylase 6b, Kdm6b In Synapse Maturation

> **NIH NIH F31** · DUKE UNIVERSITY · 2020 · $37,644

## Abstract

ABSTRACT
The development and maturation of neurons require temporal induction of cell-specific gene expression
programs. This is due in part to mechanisms of chromatin regulation that make sure the right genes are
expressed and the wrong genes are repressed at any given time. While chromatin mechanisms that regulate
neuronal differentiation early in development are well-characterized, the mechanisms in maturing fate-committed
neurons are much less understood. One example of chromatin regulation is the trimethylation of lysine 27 on
histone H3, which is a mark associated with gene repression and functions early on in development to prevent
the expression of genes involved in alternative cell-fate determination. Our lab has shown that H3K27me3 is lost
at specific sites during neuronal maturation, suggesting that this mark undergoes dynamic regulation over time.
Thus, we raised the possibility that regulation of H3K27me3 by chromatin regulators can underlie neuronal
maturation. Taking advantage of a well-defined model of neuronal development, the rodent cerebellum, I will
characterize the role of Kdm6b, a lysine-specific demethylase involved in demethylating H3K27me3, in cerebellar
maturation. Our lab has shown that loss of Kdm6b in cerebellar granule neurons (CGNs) results in a disruption
of a mature gene expression program which includes many synaptic genes. Consistent with this, knockdown of
Kdm6b in vivo in CGNs resulted in decreased density of PSD-95, a marker for the postsynapse. Thus, I
hypothesize that Kdm6b regulates CGN synapse maturation through the temporal induction of this mature gene
expression program. Utilizing a combination of powerful genetic tools and molecular biochemistry, I plan to study
how loss of Kdm6b affects CGN synapse maturation in a cell-autonomous fashion in vivo over time, as well as
dissect the mechanism by which Kdm6b regulates CGN gene expression. Completion of these two aims will
define to what extent can changes in gene expression and chromatin regulation manifest as cellular changes in
maturing fate-committed neurons. Additionally, this proposal will elucidate exactly how Kdm6b regulates genes
to mediate downstream cellular changes.

## Key facts

- **NIH application ID:** 10063435
- **Project number:** 5F31NS113394-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Urann Chan
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,644
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063435

## Citation

> US National Institutes of Health, RePORTER application 10063435, The Role of the Lysine-Specific Histone Demethylase 6b, Kdm6b In Synapse Maturation (5F31NS113394-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10063435. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*