# Chromatin-mediated mechanisms of transcription regulation in ES cells

> **NIH NIH R35** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $383,340

## Abstract

PROJECT SUMMARY/ABSTRACT
 Our research interests focus on the similarities and differences in chromatin structure among different
cell types and how chromatin remodeling 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.
 Approximately 75% of the mammalian genome is transcribed. While coding regions account for only
~2% of the genome, the remaining intergenic and intragenic transcription generates a large collection of non-
coding RNAs (ncRNAs). Two regions rich with non-coding transcription are active enhancers (where ncRNAs
are generated bi-directionally) and promoters (where ncRNAs are generated in the antisense orientation from
protein-coding genes). While a few individual ncRNAs have been shown to function in gene activation, their
activities in gene regulation have not been systematically addressed. Recently, we showed that esBAF, a
nucleosome remodeling complex that binds enhancers and promoters, is necessary for repression of
numerous ncRNAs throughout the genome in ES cells. Upon depletion of esBAF, nucleosome occupancy
flanking regions of open chromatin was reduced, resulting in elevated ncRNA transcription. Based on these
studies, we are in a unique position to build a network of ncRNA regulation by nucleosome remodeling factors
in ES cells. Specifically, we will determine (1) how esBAF regulates higher order chromatin structure, (2) the
functions of enhancer-specific ncRNAs (eRNAs) in enhancer looping and gene regulation, (3) the mechanisms
underlying regulation of mRNAs by ncRNAs, and (4) the network of nucleosome remodeling complexes
regulating ncRNA expression. These studies will enhance our understanding of the chromatin-centered
regulation of ncRNAs.
 Over the next five years, our laboratory will identify nucleosome remodelers that regulate ncRNA
expression, explore the role of nucleosome remodeling factors in regulating higher order chromatin structure at
the level of enhancer-promoter looping, and determine the function of two uncharacterized classes of ncRNAs
in ES cells. The proposed research is significant because it will uncover fundamental mechanisms that
choreograph the interplay of chromatin dynamics with ncRNA function, consequently providing a crucial step in
understanding ES cell fate decisions.

## Key facts

- **NIH application ID:** 10001562
- **Project number:** 5R35GM133732-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sarah Jane Hainer
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,340
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001562

## Citation

> US National Institutes of Health, RePORTER application 10001562, Chromatin-mediated mechanisms of transcription regulation in ES cells (5R35GM133732-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001562. Licensed CC0.

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