# Role of Chromatin Structures in Genomic Imprinting

> **NIH NIH F32** · HARVARD UNIVERSITY · 2024 · $74,284

## Abstract

PROJECT SUMMARY
Genomic imprinting is an epigenetic phenomenon in which somatic genes are mono-allelically expressed
depending on their parental origin. Imprinted genes play critical roles in prenatal and postnatal development,
including growth, metabolism, and neurodevelopment. Thus, genomic imprinting is essential for organismal
viability, and disrupted imprinting frequently results in human disease. Imprinted genes are abundantly
expressed in the brain; however, investigation into their regulatory mechanisms and physiological significance
in the brain has been limited. Emerging evidence suggests that chromatin structure at imprinted domains may
differ between the two parental alleles, implying a mechanistical model where differential chromatin structures
may confer allele-specific regulatory roles. Nevertheless, the exploration of the impact of allele-specific chromatin
structure on imprinted gene regulation is still in its early stages. The Mest-Copg2 imprinted domain, located on
mouse chromosome 6 and human chromosome 7, presents a neuron-specific imprinting pattern and is
associated with developmental and postnatal growth defects and atypical maternal behavior. In preliminary data,
striking differences in parental chromatin structures at the Mest-Copg2 domain were observed. Yet, the extent
to which chromatin structures play a role in imprinted expression of Mest-Copg2 remains entirely uncharted.
Thus, this proposed research delves into the regulatory mechanism and functional role of the Mest-Copg2
domain. The focus of Aim 1 will be elucidating how allelic chromatin structures are established in the Mest-
Copg2 domain. Epigenetic perturbation tools will be used to establish what are the basis of allelic chromatin
structures in this domain. Aim 2 will identify cis-regulatory elements modulating Mest-Copg2 imprinted
expression. CRISPRi experiments will be conducted in hybrid primary neurons to validate the activities of cis-
regulatory elements in mediating imprinted Mest-Copg2 expression. In Aim 3, the physiological implication of
neuron specific Copg2 imprinting will be investigated to provide insights into the role of genomic imprinting in
neurons. These results will provide a novel regulatory mechanism mediated by chromatin structure, as well as
functional implication of genomic imprinting in the Mest-Copg2 domain. The Harvard University will provide a
vibrant research atmosphere with ample opportunities for inter- and intradepartmental collaborations. This
environment, coupled with the guidance of Dr. Whipple and Dr. Dulac, will provide valuable training opportunities
to develop scientific and professional skills necessary for becoming an independent researcher.

## Key facts

- **NIH application ID:** 10996265
- **Project number:** 1F32GM156080-01
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Bong Min Bae
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,284
- **Award type:** 1
- **Project period:** 2024-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996265

## Citation

> US National Institutes of Health, RePORTER application 10996265, Role of Chromatin Structures in Genomic Imprinting (1F32GM156080-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10996265. Licensed CC0.

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