# Chromatin-mediated mechanisms of transcription regulation in ES cells

> **NIH NIH R35** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $407,335

## Abstract

PROJECT SUMMARY/ABSTRACT
 Stem cells have the unique property to self-renew or differentiate into any of the 200+ different cell types
of the body. Understanding the mechanisms that contribute to stem cell identity and specific cellular
differentiation is essential to direct them to specialized cell states which can then be utilized for targeted therapy
for countless diseases. There has been increased interest in understanding the role of chromatin regulatory
factors in stem cell identity due to their essential roles in cellular processes and during development. During
development, lineage specification is accompanied by genome-wide chromatin reorganization and gene
expression pattern changes. Therefore, it is not surprising that epigenetic factors represent one of the largest
protein classes that are mutated in disease states, including developmental disorders. Our research interests
focus on the similarities and differences in chromatin structure among different cell types and how chromatin
regulatory factors that modulate these differences regulate cell fate. The long-term goals of our laboratory are to
comprehensively understand the functions, targets, regulation, and mechanisms of action of non-coding RNAs
(ncRNAs) and chromatin regulatory factors with critical functions in gene regulatory networks.
 Here, we propose three related but distinct research directives. We will determine the mechanism through
which FACT, an essential histone chaperone, acts to maintain embryonic stem (ES) cell identity. We propose
FACT is regulating cis regulatory elements (CREs) by modulating chromatin structure and transcription factor
(TF) binding to regulate transcription of genes required to maintain stem cell identity. In parallel, we will capitalize
on our system biology approach of understanding how nucleosome remodeling complexes contribute to cell
identity through ncRNA regulation. To that end, we will examine the functional interactions among understudied
nucleosome remodeling complexes, including how some remodelers may compensate for loss of another or
work redundantly. Finally, we will uncover the molecular contribution of an essential epigenetic factor, BAF, in
neural differentiation focusing, in part, on the complexes role in regulating non-coding transcription.
 Over the next five years, our laboratory will define the mechanism of FACT function in ES cells, determine
the interplay between a subset of nucleosome remodelers in gene regulatory networks, and understand the
contribution of one remodeler in regulating differentiation. The proposed research is significant because it will
uncover fundamental mechanisms that choreograph the interplay of chromatin dynamics with ncRNA function,
providing a crucial step in understanding cell fate decisions.

## Key facts

- **NIH application ID:** 10840676
- **Project number:** 2R35GM133732-06
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sarah Jane Hainer
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $407,335
- **Award type:** 2
- **Project period:** 2019-09-17 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840676

## Citation

> US National Institutes of Health, RePORTER application 10840676, Chromatin-mediated mechanisms of transcription regulation in ES cells (2R35GM133732-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10840676. Licensed CC0.

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