# Epigenetic regulation of cell identity by PRC1 complexes

> **NIH NIH R35** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $395,800

## Abstract

Abstract
One of the fundamental questions in biology and by extension, stem cell-based regenerative medicine, is how
cell fate is determined in multicellular organisms. Both genetic pathways and epigenetic programs play key
roles in lineage specification during the embryonic development of vertebrates. As an important advance, we
recently discovered an epigenetic network constituted by a large family of complexes formed by Polycomb
group (PcG) proteins. PcG proteins form two major groups of Polycomb repressive complexes (PRCs), PRC1
and PRC2. Even though PRC1 and PRC2 are generally involved in gene repression, mammalian components
of PRC1 complexes are exceptionally diverse and their functions are poorly understood. Despite substantial
evidence supporting the involvement of PRC1 in cell fate determination, little is known about how the family of
mammalian PRC1 complexes coordinates its regulation of lineage specification. This is largely due to the great
heterogeneity inherent in the composition of PRC1 complexes in mammals. We propose two independent yet
complementary projects to resolve this knowledge gap. Project 1 will elucidate the roles of mammalian PRC1
complexes in cell identity determination. We will utilize a novel approach recently developed by our team to
trace the compositional changes of PRC1 complexes in a lineage specific manner and combine this with
proteomic, biochemical, and genomic studies. Project 2 will reveal the molecular mechanisms underlying
PRC1 complex-mediated transcriptional regulation. This will be accomplished through biochemical analyses
and the targeting of individual PRC1 complexes in cells. Taken together, our studies will generate important
mechanistic insights into the epigenetic regulation of cell identity, an essential requirement for improving stem-
cell based regenerative therapeutic techniques. These approaches also will provide new opportunities to
understand the functional diversity of protein complexes in a wide variety of biological processes.

## Key facts

- **NIH application ID:** 10224765
- **Project number:** 5R35GM133496-03
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** ZHONGHUA GAO
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $395,800
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10224765

## Citation

> US National Institutes of Health, RePORTER application 10224765, Epigenetic regulation of cell identity by PRC1 complexes (5R35GM133496-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10224765. Licensed CC0.

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