# Histone Demethylase Control of Post Implantation Development

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $396,063

## Abstract

ABSTRACT
Functional specialization in a multicellular organism arises when cell fate is established by a specific gene
expression pattern. Epigenetic modifications working with transcription factors enable cell identity. During early
development a few cells migrate at the epiblast stage to the gonad to become Primordial germ cells (PGCs),
which are the precursors of gametes. PGCs undergo an ordered series of global epigenetic changes that
decimates the repressive modifications: H3 lysine 9 methylation (H3K9me2) and DNA methylation, which
suppress expression of repetitive elements to maintain genomic integrity, and is replaced by other marks such
as H2A/H4 arginine methylation (H2A/H4R3me2). How the precise temporal regulation of these epigenetic
events is coordinated and their interdependence remains poorly understood. Incorrect or partial erasure at
specific locations could lead to imprinting defects as well as inadvertent transgenerational inheritance. We
have discovered that the H3K9me2 demethylase, KDM3B, controls DNA demethylation by the Tet enzymes
and interacts with PRMT5, a H2A/H4R3 methyltransferase. Despite H3K9me2 being a repressive histone
modification, we have found that KDM3B and KDM3A interact with mRNA processing machinery. Taken
together we hypothesize that proteins of the KDM3 family orchestrate post-implantation development to PGCs
by epigenetic and post-transcriptional mechanisms, which will be investigated in this proposal.

## Key facts

- **NIH application ID:** 10367127
- **Project number:** 1R01HD105151-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Rupa Sridharan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $396,063
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367127

## Citation

> US National Institutes of Health, RePORTER application 10367127, Histone Demethylase Control of Post Implantation Development (1R01HD105151-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10367127. Licensed CC0.

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