# Biochemical, Genomic and Computational Analysis of Transcriptional Repression

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2020 · $309,955

## Abstract

Project Summary
Transcriptional repressors represent the necessary counterweight to transcriptional activators in metazoan
development. The mechanisms of transcriptional repression have been intensively investigated, but we lack
crucial insights into how repressors act at a mechanistic level across many targets in the genome. In particular,
the coordinated recruiting of transcriptional co-repressors can generate diverse effects on chromatin structure
and modification, and we still lack insights on the functional significance of many changes that can be
measured in `omics studies. To develop key insights into eukaryotic transcriptional regulatory mechanisms, we
use the natural setting of the Drosophila embryo to identify basic biochemical processes in a developmental
setting, where differential gene expression is used to drive the developmental fate of particular cells and
tissues. In this proposal, 1) we will use genome-wide methods developed in our laboratory to identify direct
biochemical, chromatin-based processes that are directed by a set of five endogenous transcriptional
regulators that repress through short-range and long-range mechanisms. 2) We will study the in vivo activity of
wild-type and mutant repression complexes to identify the contributions of distinct transcriptional co-repressors
Groucho and CtBP, testing their contributions to quantitative and/or qualitative effects in chromatin
modifications and gene regulation. 3) To identify the cis-regulatory context in which transcriptional repressors
act on different enhancers, we will quantitatively measure and mathematically model the output of specific
enhancers to uncover the fundamental quantitative properties of specific classes of repressors interacting with
activators – i.e. the common “rules” by which these proteins interact on many target genes. The three
interrelated aims will provide predictive tools for interpretation of genomic cis regulatory content of the
metazoan genome, providing essential underpinnings for studies of evolution and disease in higher
eukaryotes.

## Key facts

- **NIH application ID:** 9994942
- **Project number:** 5R01GM124137-04
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** David N Arnosti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $309,955
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994942

## Citation

> US National Institutes of Health, RePORTER application 9994942, Biochemical, Genomic and Computational Analysis of Transcriptional Repression (5R01GM124137-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9994942. Licensed CC0.

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