# Transcriptional silencers inDrosophila

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $657,639

## Abstract

In metazoans, gene expression is regulated in a tissue/cell-type-specific manner predominantly via stretches of
noncoding sequence referred to as cis regulatory modules (CRMs). CRMs contain 1 or more DNA binding sites
for 1 or more sequence-specific, regulatory transcription factors that function to modulate the expression of
target gene(s). CRMs that activate gene expression are typically referred to as enhancers, while those that
repress gene expression are referred to as silencers. Transcriptional enhancers activate gene expression in a
tissue-specific manner in development and also in adult cells in response to cellular or environmental stimuli.
Like enhancers, silencers can function in a cell-type-specific manner. Indeed, silencers may contribute a
crucial role in the specification of precise gene expression patterns, thus enabling the establishment of sharp
expression domains, such as during development.
Numerous genomic and computational studies have focused primarily on predicting and characterizing
enhancers. In contrast to enhancers, silencers are much less well understood. Few transcriptional silencers
have been described, and there have been no large-scale efforts to catalog silencers nor to identify predictive
features of silencers, such as chromatin marks. The overarching goals of this project are to identify and
quantify the activities of tissue-specific silencers, to identify the chromatin signatures of silencers, and to
elucidate the regulatory roles of silencer-associated (co-)repressors and DNA sequence motifs. In pursuing
these goals, we will develop novel “quantitative silencer-FACS-Seq” technology for quantitative screening of
CRMs for tissue-specific silencer activity, and BioTAP-XL-TALE technology for identification of proteins found
in tissue-specific chromatin assembled at specific cis-regulatory elements in cells where they act as silencers
versus in cells where they act as enhancers. We will focus on the developing embryonic mesoderm in
Drosophila melanogaster as our model system. We anticipate that the features and chromatin signatures of
silencers identified in this project will be evolutionarily conserved across metazoans, including human.

## Key facts

- **NIH application ID:** 9934877
- **Project number:** 5R01HG009723-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** MARTHA L BULYK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $657,639
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934877

## Citation

> US National Institutes of Health, RePORTER application 9934877, Transcriptional silencers inDrosophila (5R01HG009723-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934877. Licensed CC0.

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