# The roles of conserved domains of proteins from the BET family in transcriptional regulation

> **NIH NIH P20** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2022 · $341,000

## Abstract

Accurate control of gene transcription is necessary for most cellular processes and dysregulation of 
transcription underlies development and progression of many human diseases. Gene transcription is 
regulated by a complex interplay of sequence-specific transcription factors, coactivator complexes, and 
chromatin landscape. Chromatin readers are regulatory factors which translate modifications on histone 
tails into specific transcriptional output. Most chromatin readers are subunits of large protein complexes 
which remodel or modify chromatin. One of the exceptions is a bromodomain and extra-terminal domain 
(BET) protein family. BET proteins are characterized by the presence of two bromodomain which allows 
them to recognize acetylated lysine residues and an extraterminal (ET) domain which was proposed to 
support protein-protein interactions. BET family members are conserved across eukaryotes from yeast to 
humans and are required for maintaining global transcriptional programs in both healthy and diseased 
cells. Consequently, BET proteins are a promising drug target for many human pathologies. Despite their 
essential function in transcriptional regulation the specific roles of BET proteins are not well understood. 
BET proteins have a modular architecture which includes bromodomains, ET domain and several other 
highly conserved domains of mostly unknown biological significance. Our central hypothesis, supported 
by preliminary data, assumes that BET protein domains other than bromodomains are important for the 
roles of BET proteins in transcriptional regulation. We propose to employ the yeast model system for a 
comprehensive investigation into the functions of all BET domains conserved between yeast and human 
cells. Building on our prior work, we will focus on the mechanisms which direct BET protein association 
with chromatin and participation of BET proteins in transcription initiation. We speculate that BET proteins 
provide an interaction hub for recruitment of coactivator complexes during transcription initiation, and we 
expect that specific domains of BET factors contribute to these activities. The results of the project will 
significantly expand the models of transcriptional regulation in both yeast and human cells. 
Characterization of the functions of individual BET protein domains may also lead to identification of 
promising drug targets to modulate aberrant transcription and offer an alternative to non-selective 
inhibition of BET bromodomains.

## Key facts

- **NIH application ID:** 10757192
- **Project number:** 5P20GM103636-10
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** RAFAL DONCZEW
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $341,000
- **Award type:** 5
- **Project period:** 2022-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757192

## Citation

> US National Institutes of Health, RePORTER application 10757192, The roles of conserved domains of proteins from the BET family in transcriptional regulation (5P20GM103636-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10757192. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*