# Transcriptional silencers in Drosophila

> **NIH NIH R56** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $691,870

## Abstract

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.
Genomic and computational studies traditionally have focused primarily on predicting and characterizing
enhancers. Silencers have been investigated far less and are much less well understood. The overarching
goals of this project are to identify and quantify the activities of tissue-specific silencers and their potential
bifunctionality as enhancers in alternate cellular contexts, to identify the chromatin signature(s) of silencers, to
determine whether silencers exhibit specificity in terms of the promoter and/or enhancer context within which
they reduce gene expression, and to elucidate the regulatory roles of silencer-associated repressors,
corepressors and DNA sequence motifs. We will also characterize the chromosomal contacts of silencers that
are mediated by repressors bound at different classes of silencers. In pursuing these goals, we will develop
novel technology for quantitative assays of elements for tissue-specific silencer activity in the context of various
enhancer-promoter combinations, and novel 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:** 11139982
- **Project number:** 2R56HG009723-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** MARTHA L BULYK
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $691,870
- **Award type:** 2
- **Project period:** 2017-08-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11139982

## Citation

> US National Institutes of Health, RePORTER application 11139982, Transcriptional silencers in Drosophila (2R56HG009723-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11139982. Licensed CC0.

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