# Investigating Novel Modes of Epigenetic Regulation Through the Polycomb Group

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $415,585

## Abstract

Abstract
The objective of this proposal is to illuminate epigenetic transcriptional regulation during mouse embryogenesis
and stem cells through investigations of the Polycomb group. The Polycomb group comprises a prominent set
of histone modifiers that are essential for the execution of diverse developmental processes, including X-
chromosome inactivation, self-renewal and differentiation of embryonic stem cells, cell and tissue specification,
and body patterning in mammals. The Polycomb repressive complex 2 (PRC2) catalyzes histone H3K27me3
through the methyltransferases EZH2 and its paralog EZH1. H3K27me3 functions as a key epigenetic mark in
development and is dysregulated in human diseases. Through much work in Drosophila, PRC2-catalyzed
H3K27me3 has been shown to epigenetically maintain transcriptional silencing. Through preliminary
investigations in early mouse embryos, we propose that PRC2 may also initiate transcriptional silencing. In
Aim 1, we will therefore test the role of PRC2 in initiating epigenetic transcriptional silencing. We have further
found the PRC2 protein EED can function independently of PRC complexes to execute epigenetic silencing in
early embryos and in embryo embryo-derived stem cells. In Aim 2, we will define the non-PRC role of EED in
epigenetic silencing in preimplantation mouse embryos and its derived stem cells. Finally, countering the
prevailing dogma that H3K27me3 is deposited solely by PRC2 our results demonstrate an additional
H3K27me3 catalyst. In Aim 3, we propose to identify and dissect the function of a novel H3K27me3 catalyst in
extra-embryonic and embryonic stem cells. All three Aims utilize unbiased approaches to define novel
functions and mechanisms of PRC2 proteins and H3K27me3 catalysis during mouse embryogenesis and in
early embryo-derived stem cells. Our central hypothesis is that the mode of epigenetic regulation ascribed to
the Polycomb group can occur via alternate mechanisms and proteins. The expected findings will increase our
understanding of the epigenetic logic underlying embryonic development and how epigenetic dysregulation
contributes to human disease.

## Key facts

- **NIH application ID:** 10396014
- **Project number:** 5R01HD095463-05
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** SUNDEEP KALANTRY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $415,585
- **Award type:** 5
- **Project period:** 2018-07-05 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10396014

## Citation

> US National Institutes of Health, RePORTER application 10396014, Investigating Novel Modes of Epigenetic Regulation Through the Polycomb Group (5R01HD095463-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10396014. Licensed CC0.

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