# Comprehensive Mapping of Long-Range Chromatin Interactions in Humanand Mouse Genomes

> **NIH NIH UM1** · JACKSON LABORATORY · 2021 · $1,949,357

## Abstract

PROJECT SUMMARY/ABSTRACT
Efforts to map the functional elements of the human genome, which include elements such as insulators,
enhancers, promoters and transcriptional start sites, have historically treated the genome as linear. However, it
is now well appreciated that the genome has a three-dimensional (3D) organization that is important for mediating
functional associations between regulatory elements and gene-coding sequences. Thus a linear map provides
an incomplete picture of the genome, and it is often difficult or impossible to infer functional associations between
regulatory elements without a topological framework to provide context. We have developed and advanced a
powerful, high-resolution method for providing such a topological framework, Chromatin Interaction Analysis
using Paired-End Tag sequencing (ChIA-PET). Using ChIA-PET, we have demonstrated that specific DNA motifs
bound by CCTC-binding Factor (CTCF) are critical in defining topological domains and arranging the gene
positions for coordinated transcription mediated by RNA Polymerase II (RNAPII). Therefore, the combination of
CTCF and RNAPII ChIA-PET will be effective for comprehensively mapping the major structure codes and
topological organization that scaffold RNAPII associated transcriptional regulation. We will contribute ChIA-PET
technology to the ENCODE Project to both strengthen existing ENCODE datasets and identify new “structure
code” elements and their interplays with gene-coding sequences that will aid in understanding the transcriptional
landscape of the genome.
We have established a robust ChIA-PET pipeline from library production to data processing for human and
mouse cells. Here, we propose to apply this platform to assay large numbers of cell lines and primary cells that
represent a wide-range of cellular space with important biological significance. Based on our current production
scale and estimated budget allocation, we aim to produce 1024 high quality datasets from CTCF and RNAPII
ChIA-PET experiments, each with two biological replicates for 256 biological samples. This pipeline capacity will
be applied to samples selected by the ENCODE Consortium, and to this sample pool we aim to contribute a
collection of high value biological samples that are likely of common interest to both the Consortium and the
greater research community. These samples include both primary and in vitro–differentiated human blood cells,
healthy and diseased induced pluripotent stem cells (iPSC), mature neurons differentiated from the iPSCs, and
several major cell and tissue types from healthy and disease-model mice. These samples were selected to
expand the “cell space” explored by the ENCODE Project and also because ChIA-PET analyses will be
particularly relevant for revealing fundamental biology.

## Key facts

- **NIH application ID:** 10241034
- **Project number:** 3UM1HG009409-04S1
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** CHARLES LEE
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,949,357
- **Award type:** 3
- **Project period:** 2017-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241034

## Citation

> US National Institutes of Health, RePORTER application 10241034, Comprehensive Mapping of Long-Range Chromatin Interactions in Humanand Mouse Genomes (3UM1HG009409-04S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10241034. Licensed CC0.

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