# Revealing the Defects in Gene Regulation that Link ARID1B to a Spectrum of Neurodevelopmental Disorders

> **NIH NIH F31** · EMORY UNIVERSITY · 2024 · $48,974

## Abstract

PROJECT SUMMARY
Neurodevelopmental disorders (NDD) are a group of highly prevalent conditions that affects 1-10% of children
in the United States. These disorders are highly heterogenous and present with a wide range of cognitive, social,
and behavioral deficits. One of the most commonly mutated genes in NDD is ARID1B, which encodes a subunit
of the BRG1/BRM-Associated Factor (BAF) chromatin remodeling complex. BAF complexes establish regions
of accessible chromatin at non-coding cis-regulatory elements (cREs) in the genome, which initates gene
transcription. ARID1B is one of the most enriched genes for de novo mutations in NDD patients, and ARID1B
mutations cause NDDs with a variety of phenotypic manifestations. However, it is not well understood how de
novo coding mutations in ARID1B impact the gene regulatory networks during neuronal development that lead
to NDDs. While de novo mutations in ARID1B lead to NDDs, many NDD patients do not present with a coding
mutation in ARID1B. Genomic studies have shown an excess of de novo mutations in putative cREs in NDD
cohorts, implicating non-coding mutations in the pathogenesis of these disorders. While there is a strong
indication of mutations in cREs in NDDs, the location of cREs that direct the translation of ARID1B are not known,
nor looked at for de novo mutations that can cause NDDs. To bridge these gaps in knowledge, I will investigate
the impact of coding and non-coding mutations in ARID1B on neuronal development. To this end, I will
characterize Arid1b halpoinsufficient mice at the single-cell level that are known to exhibit behavioral and
morphological deficits reminiscent of those seen in NDD patients. This will allow me to identify patterns of
dysregulation to chromatin accessibility and gene expression at multiple timepoints of development. I will also
identify putative enhancer regions of ARID1B using chromatin interaction and single-cell(sc) co-accessibility
datasets. With these data I will be able to characterize enhancers that regulate ARID1B expression. Moreso,
with these data I will identify an enrichment of de novo mutations in enhancers of ARID1B that lead to NDDs.
This work will provide a better understanding of how mutations in coding and non-coding regions of ARID1B and
dysregulate critical molecular mechanisms necessary for normal neuronal development during embryogenesis
that leads to NDDs.

## Key facts

- **NIH application ID:** 10901583
- **Project number:** 1F31HD112113-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** YONINA LOSKOVE
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-05-02 → 2027-05-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901583

## Citation

> US National Institutes of Health, RePORTER application 10901583, Revealing the Defects in Gene Regulation that Link ARID1B to a Spectrum of Neurodevelopmental Disorders (1F31HD112113-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10901583. Licensed CC0.

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