# Epigenetic Regulation of Kidney Development

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $351,000

## Abstract

ABSTRACT
Gene expression patterns define the differentiated state of cells and their physiological
functions. During embryonic development, gene expression patterns are set, in part, by
epigenetic modifications that compartmentalize the genome into active euchromatin and
silent heterochromatin. These modifications include histone and DNA methylation,
which imprint a unique cell-type specific pattern on the epigenome such that cellular
fates and phenotypic stability are maintained. In diseased states, the normal pattern of
gene expression is disturbed which can result in altered cellular function, growth
deregulation, abnormal cell signaling, and cell death. This competitive renewal
application proposes that epigenetic changes can underlie the alterations in gene
expression patterns observed in both acute and chronic renal disease. In the previous
funding period, the PI has identified Pax2 as a critical DNA binding protein in the renal
epithelial lineage. The lab then discovered PTIP as an adaptor protein that links Pax2 to
a histone methylation complex to imprint positive epigenetic marks on target genes. The
PTIP protein interacts with a variety of DNA binding proteins to recruit an MLL3/4 histone
H3K4 methyltransferase complex to chromatin. This Pax2/PTIP interaction can be
inhibited by the repressor proteins of the Tle/Groucho family, which are expressed in
more differentiated renal epithelial cells. The current application will address how
epigenetic regulators impact the fate of renal epithelial cells and renal interstitial
fibroblasts in both acute and chronic disease states. Preliminary data strongly suggests
that epigenetic modifications are needed to reset the proper transcriptional program of a
renal epithelial cell during regeneration after acute injury. Our first specific aim will
address the need for epigenetic modifiers in promoting regeneration and maintaining
renal epithelia after injury. The second aim will address changes in renal interstitial
fibroblasts or stromal cells in response to acute or chronic injury. The expansion of
fibroblasts and myofibroblasts is a common pathology observed in the kidney and other
tissues in chronic, progressive diseases. Yet, in limited cases the fibrosis is reversible.
The reversibility suggests some type of epigenetic memory that may be altered in the
case of irreversible fibrotic disease. What are the differences in gene expression and
epigenetic modifications between a myofibroblast that defines an irreversible,
progressive disease state and one that can be reversible? The answers to this question
will reveal potential novel pathways that control phenotypic stability, cell proliferation,
and disease progression in a variety of abnormal states. Given the limited treatment
options currently available for chronic renal disease, understanding the epigenetic level
of control in the disease state is paramount for developing new therapeutic options.

## Key facts

- **NIH application ID:** 9954023
- **Project number:** 5R01DK073722-14
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Gregory R Dressler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $351,000
- **Award type:** 5
- **Project period:** 2006-07-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954023

## Citation

> US National Institutes of Health, RePORTER application 9954023, Epigenetic Regulation of Kidney Development (5R01DK073722-14). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9954023. Licensed CC0.

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