# Analysis of combinatorial cis-regulation in synthetic and genomic promoters

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $425,251

## Abstract

Project Summary
 When genes move to new chromosomal locations they are often expressed at drastically
different levels. We will use these chromosome position effects to investigate how different
chromosomal locations affect the activity of cis-regulatory sequences (CRS). We propose to
measure how the activities of a large and diverse collection of CRS change when they are
moved to different chromosomal locations (Aim 1). To collect this data at scale we will introduce
a new massively parallel reporter gene assay (MPRA). We aim to address several questions.
1. What accounts for the differences in regulatory potential between chromosome
 positions? When the activity of a CRS changes because it moves to a new location, are
 the changes due to the new chromatin state, the activity of nearby enhancers, or both?
2. When are the regulatory effects of CRS and genome position independent and when do
 they interact in complex ways? Do interactions depend on the properties of CRS and the
 specific chromatin landscape?
 We also propose to complement our investigation of gene expression levels with a study
of how genome position influences gene expression dynamics (Aim 2). By measuring the cell-
to-cell patterns of mRNA generated by different CRS at different chromosome locations, we will
uncover how chromosome environments alter the dynamics of expression. The successful
completion of the aims of this proposal will result in a quantitative and molecular understanding
of the combinatorial regulation of gene expression by CRS and chromatin environment. A clear
understanding of how CRS function in the genome will help identify and interpret disease-
causing genetic variants that affect cis-regulation.

## Key facts

- **NIH application ID:** 10225563
- **Project number:** 5R01GM092910-11
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Barak A Cohen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $425,251
- **Award type:** 5
- **Project period:** 2011-01-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225563

## Citation

> US National Institutes of Health, RePORTER application 10225563, Analysis of combinatorial cis-regulation in synthetic and genomic promoters (5R01GM092910-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225563. Licensed CC0.

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