# Deciphering Transcription Factor-Coregulator Interactions through Innovative Tools

> **NIH NIH R35** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $390,000

## Abstract

ABSTRACT
Transcription factors and their coregulators are pivotal in directing gene regulation,
cellular differentiation, and disease progression. Acting as molecular switches, these
complexes shape cellular fate during embryonic development, maintain tissue
homeostasis, and steer responses to environmental cues. However, disruptions in these
interactions can lead to altered gene expression, paving the way for disorders ranging
from metabolic imbalances to neurodegenerative conditions. Recognizing the need to
study the regulatory dynamics of transcription factors, we developed a proteomics method
called RIME. This technique immuno-precipitates epigenetic complexes using antibodies
and employs mass spectrometry to pinpoint members of specific protein complexes.
Nonetheless, RIME and other similar methods grapple with challenges like low
reproducibility and constraints on low-input samples. Over the next five years, our
ambition is to pioneer technologies that revolutionize the study of these complexes. A
significant shift will be transitioning from mass spectrometry to DNA barcode methods,
enhancing signal specificity from individual proteins. Our objective is to devise
instruments that bypass sample limitations and inconsistencies introduced by mass
spectrometry. Present methods only offer a mean signal for all interactors of a protein,
even though it may participate in various distinct complexes. Through our proposal, we
plan to craft DNA oligo-based techniques that amplify protein signals and discern which
members coexist in the same complex. Beyond tool development, we will apply our
methodologies to decipher dynamic shifts in transcription factor complexes, specifically
at regulatory elements like enhancers. Our proteomic instruments will seamlessly
complement state-of-the-art single-cell multi-omic methods that we are currently
employing, enhancing our understanding of how chromatin accessibility, DNA
methylation, and transcriptional patterns are influenced by epigenetic complexes.

## Key facts

- **NIH application ID:** 10937906
- **Project number:** 1R35GM154834-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Hisham Mohammed
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,000
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937906

## Citation

> US National Institutes of Health, RePORTER application 10937906, Deciphering Transcription Factor-Coregulator Interactions through Innovative Tools (1R35GM154834-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10937906. Licensed CC0.

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