# Genome-wide structural organization of proteins within human gene regulatory complexes

> **NIH NIH R01** · PENNSYLVANIA STATE UNIVERSITY, THE · 2020 · $319,962

## Abstract

The DNA sequence of the human genome informs us as to the composition of proteins that make up
healthy cells, but also altered compositions that create diseased cells. How protein production is controlled
through the regulation of the genes that encode them is of critical importance for healthy and diseased cells.
Knowing precisely where gene regulatory proteins bind, and are organized throughout the genome, including
their interactions with each other, informs us as to how genes are regulated and mis-regulated. Since there are
potentially thousands of different kinds of regulatory proteins and thousands of different kinds of human cell
types and environmental responses that are a product of various subsets of regulatory proteins, the entire
“universe” of gene regulatory events is quite substantial and consequently, quite costly to identify. A subset of
these events will likely be informative or diagnostic of diseases states. Therefore, an important goal is to define
informative interactions using cost-enabling, high accuracy, and robust genome-wide assays. To this end,
ChIP-exo was developed to map the genomic binding locations of gene regulatory proteins at near-single base
pair resolution. This assay will be applied, in high throughput, to determine the genome-wide positional
organization of factors within protein-DNA complexes, like enhanceosomes. By broadly mapping the various
classes of proteins that constitute much of the regulated epigenome, general rules about enhancer and
repressor complex organization will be deduced. Aim 1 involves collecting genome-wide ChIP-exo data in
human cell lines for a wide variety of protein-DNA complexes. Aim 2 will develop and implement
computational approaches towards pattern recognition and data distillation in ChIP-exo datasets. The results
are expected to provide structural insights into macromolecular protein complex assembly on a genomic scale,
and in various cell types and conditions.

## Key facts

- **NIH application ID:** 9840489
- **Project number:** 5R01GM125722-03
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **Principal Investigator:** Shaun Aengus Mahony
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $319,962
- **Award type:** 5
- **Project period:** 2018-01-19 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840489

## Citation

> US National Institutes of Health, RePORTER application 9840489, Genome-wide structural organization of proteins within human gene regulatory complexes (5R01GM125722-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9840489. Licensed CC0.

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