# Mechanistic study of pioneer factors

> **NIH NIH R01** · PENNSYLVANIA STATE UNIVERSITY, THE · 2020 · $295,240

## Abstract

Project Summary
In eukaryotic cells, nucleosomes prevent efficient binding of transcription factors and transcription machinery to
their genomic targets. A special group of transcription factors called “pioneer factors” can invade compact
chromosome and remodel nucleosomes near their binding sites, allowing the access of transcription factors
and triggering their transcriptional competency. Pioneer factors play critical roles in gene regulation and cell
differentiation. Mutation or mis-regulation of pioneer factors are associated with developmental diseases and
many types of human cancer.
Despite their essential functions, the mechanism underlying the pioneer activity is unclear. Our long-term goal
is to develop a detailed mechanistic understanding of how pioneer factors access their nucleosomal binding
sites, disrupt histone-DNA contacts, and activate gene expression. To achieve this goal, our overall objective in
this proposal is to quantitatively measure the binding, nucleosome-depleting, and gene regulatory activities of
pioneer factors under a variety of genetic and cellular conditions. We will perform these measurements into
three aims. At the population level, we will determine the steady-state nucleosome-depleting activities among
genome-wide TFs to understand what kind of TFs can serve as pioneers and how their nucleosome-depleting
activities are regulated in vivo (aim 1). At the single cell level, we will evaluate the gene regulatory activities of
pioneer factors and their cell-to-cell variability (aim 2). At the single molecule level, we will directly measure the
kinetics of pioneer factor binding and invasion of the nucleosome substrates in vitro (aim 3). Completion of
these aims is expected to advance the fundamental knowledge of pioneer factors and their role in chromosome
opening and gene regulation. It will also contribute to future dissection of the functional roles of pioneer factors
in cancer cells and the development of novel therapies to combat their dysfunction.

## Key facts

- **NIH application ID:** 9834956
- **Project number:** 5R01GM121858-04
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **Principal Investigator:** Lu Bai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $295,240
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9834956

## Citation

> US National Institutes of Health, RePORTER application 9834956, Mechanistic study of pioneer factors (5R01GM121858-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9834956. Licensed CC0.

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