# Roles of allele-specific chromatin interactions in transcription regulation during development

> **NIH NIH K99** · JACKSON LABORATORY · 2021 · $129,622

## Abstract

PROJECT SUMMARY / ABSTRACT
A fundamental challenge in developmental biology is to dissect how one multipotent cell differentiates into a
specific cell type. Most studies are limited to 1-dimensional genomic data that measure transcription level (RNA-
seq), protein binding intensity (ChIP-seq), and chromatin accessibility (ATAC-seq). These datasets lack direct
evidence of communication between various regulatory elements that accommodate gene regulation and
differentiation. To solve this problem, we will leverage cutting-edge 3D genome technologies, ChIA-PET and
ChIA-Drop. By enriching for specific protein factors CCCTC binding factor (CTCF) and RNA Polymerase II
(RNAPII), one can interrogate chromatin architecture and gene regulation in aggregated bulk cells (ChIA-PET)
and in a single molecule (ChIA-Drop). We will exploit the highly dissimilar genomes in F1 hybrid mouse strains
derived from mating a laboratory mouse and a wild mouse to assign high-throughput sequencing reads to
parental origin, thereby unraveling the allele-specific gene expression and chromatin interactions. We propose
to: (i) determine whether allele-specific interactions between regulatory elements and methylation status in
mouse embryonic stem cells (mESCs) drive allele-specific gene expression, (ii) quantify cell-to-cell heterogeneity
of multiplex chromatin interactions. We will subsequently differentiate mESCs into three lineage-specific
precursors ectoderm, mesoderm, and endoderm in vitro. By performing ChIA-PET, we can identify which, if any,
of the pre-established interactions among enhancers, promoters, and CTCF persist or vanish after this process.
ChIA-Drop data will potentially capture the dynamics therein. Throughout the K99 and R00 phases, we will
continue to develop computational algorithms that can: (i) quantitatively assess reproducibility of replicate
experiments, (ii) identify statistically significant differential interactions, and (iii) trace and quantify single-
molecule dynamics and heterogeneity of allele-specific multiplex interactions. To succeed in these aims, the
investigator will expand her knowledge domain to developmental biology and receive additional hands-on
experimental training in 3D genome mapping technologies and mouse embryonic stem cell culture, harvest, and
differentiation techniques. Together, these genome-wide communication links between regulatory elements and
architectural protein will provide insights into gene regulation and genomic imprinting mechanisms during
gastrulation.

## Key facts

- **NIH application ID:** 10105762
- **Project number:** 1K99HG011542-01
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Minji Kim
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $129,622
- **Award type:** 1
- **Project period:** 2021-02-05 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105762

## Citation

> US National Institutes of Health, RePORTER application 10105762, Roles of allele-specific chromatin interactions in transcription regulation during development (1K99HG011542-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10105762. Licensed CC0.

---

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