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

> **NIH NIH UM1** · JACKSON LABORATORY · 2020 · $1,967,222

## 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 CCCTC-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:** 9867735
- **Project number:** 5UM1HG009409-04
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** CHARLES LEE
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,967,222
- **Award type:** 5
- **Project period:** 2017-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9867735

## Citation

> US National Institutes of Health, RePORTER application 9867735, Comprehensive Mapping of Long-Range Chromatin Interactions in Human and Mouse Genomes (5UM1HG009409-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9867735. Licensed CC0.

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