# Dissecting the roles of an epigenetic regulator of genes involved in synaptic plasticity and social cognition.

> **NIH NIH R01** · UPSTATE MEDICAL UNIVERSITY · 2022 · $726,097

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal represents a highly innovative line of research focused on understanding the mechanism/s
by which PHF21B (plant homeodomain finger protein 21B) deficiency impairs social memory. Social
impairments, which may be present in multiple psychiatric disorders, are characterized by deficiencies in
social functioning. Social cognitive impairments are a central feature of several neurodegenerative,
neuropsychiatric, and neurodevelopmental disorders, such as autism spectrum and attention deficit
hyperactivity disorder. They also frequently occur following acute brain damage after traumatic brain injury
and stroke. We present conceptually novel evidence showing that PHF21B deficiency significantly impairs
social memory. In the three-chamber social interaction test, the social preference index of the PHF21B
deficient mice did not significantly differ, but they spent more time interacting with the new stranger than
with the familiar stranger compared to wild-type mice. Therefore, their social novelty index was
significantly greater than wild-type animals, suggesting social memory deficits. Social memory
impairments were further confirmed using the 5-trial social memory test. Our new data also support the
concept that PHF21B binds to the epigenetic marker tri-methylated Lys36 at histone H3 (H3K36me3), a
histone marker associated with expressed gene bodies and recruits proteins implicated in transcription,
splicing, and DNA repair. The proposed studies will interrogate the specific role(s) of PHF21B in neuronal
function relevant to social behaviors, specifically in social recognition impairment. Expected outcomes are
to characterize the role of PHF21B in the hippocampus and identify its target genes and regulatory
mechanisms relevant to social memory. We expect that the proposed studies will provide novel insights
into the cellular and molecular mechanisms underlying epigenetic changes that affect social recognition
memory. The results to be generated by this project have translational potential as they may facilitate the
development of novel pharmacological targets for social memory deficits.

## Key facts

- **NIH application ID:** 10446334
- **Project number:** 1R01MH127423-01A1
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Julio Licinio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $726,097
- **Award type:** 1
- **Project period:** 2022-05-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446334

## Citation

> US National Institutes of Health, RePORTER application 10446334, Dissecting the roles of an epigenetic regulator of genes involved in synaptic plasticity and social cognition. (1R01MH127423-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10446334. Licensed CC0.

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