# Deciphering the Paralogue Specific Interactions within the Sin3 Protein Interaction Network

> **NIH NIH F31** · STOWERS INSTITUTE FOR MEDICAL RESEARCH · 2020 · $21,713

## Abstract

Project Summary
The histone deacetylase (HDAC)-containing Sin3 complex is a chromatin modifier crucial for the
regulation of gene expression. Inhibitors against HDACs are currently in use for treatment against
cancer, while haploinsufficiency of SIN3A has been linked to neurological development disorders. The
Sin3/HDAC complex is composed of a core group of subunits; however, our data and others have
identified additional peripheral subunits that interact with the core in a mutually exclusive manner.
Furthermore, these peripheral subunits consist of a series of paralogues, each with documented links to
human diseases like cancer. These results indicate that there likely exist many distinct Sin3 complexes
that have yet to be defined. The possible combinations of paralogues that appear with the core complex
are difficult to discern with traditional proteomic analysis, which typically provides a list of proteins
enriched in samples compared to controls. Therefore, there is a critical need for strategies that are
capable of discerning between heterogeneous protein complexes. Here, my goal is to determine the
combinations of paralogues that interact with the core complex in their native cellular environment. I will
accomplish this goal by pursuing two specific aims. In the first specific aim, I will identify direct
interactions in the Sin3/HDAC protein interaction network using biochemical approaches and quantitative
imaging techniques in live cells. From this information, we will be able to build the first model of the Sin3
protein interaction network where direct interactions are defined in a systematic manner. In the second
specific aim, I will develop a novel dual-tagged system to investigate paralogue specific interactions in
live cells using quantitative proteomic and quantitative imaging techniques. From this aim, I will develop a
new approach for studying protein complexes when two proteins are likely competing for the same
interactions in the same cells. The successful completion of this project will significantly expand our
understanding of the diversity of Sin3 complexes in mammalian cells, which has broad implications for
chromatin remodeling in normal and diseased cellular states.

## Key facts

- **NIH application ID:** 9880286
- **Project number:** 5F31GM131536-02
- **Recipient organization:** STOWERS INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Cassandra G Kempf
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $21,713
- **Award type:** 5
- **Project period:** 2019-03-01 → 2020-11-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880286

## Citation

> US National Institutes of Health, RePORTER application 9880286, Deciphering the Paralogue Specific Interactions within the Sin3 Protein Interaction Network (5F31GM131536-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9880286. Licensed CC0.

---

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