# Transcription factors in early kidney development

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $573,034

## Abstract

Our goal is to elucidate the genetic networks controlled by Eya1 and its cofactors in nephron progenitor cell
fate specification, proliferation and differentiation. Eya1 is a transcriptional coactivator that indirectly affects
transcription through interaction with DNA-binding proteins. We have shown that Eya1 forms a key
transcriptional complex with: (1) the homeodomain transcription factor Six family members Six1/4 to specify
the metanephric mesenchyme (MM), and (2) Six2 and Myc in the nephron progenitors to maintain and
renew the progenitors. Through mass spectrometry analysis, we have identified the components of the
SWI/SNF chromatin remodeling complex as Eya1's interacting proteins. While chromatin remodelers are
known to regulate gene expression by altering chromatin structure and facilitating recruitment of essential
factors required for transcription, it remains unclear whether the SWI/SNF complex interact with Eya1 as
well as other factors to confer specific transcriptional programs that ensure the MM specification and
nephron formation. This application proposes to take genetic, genomic, molecular and transgenic
approaches to systematically test the hypothesis that Eya1 interacts with the SWI/SNF chromatin
remodeling complex and other partner transcription factors to create a combinatorial code that activates
gene transcription to specify a nephron fate, dictate the nephron progenitors to either self-renew or undergo
differentiation, and determine nephron segmental identity. Specifically, we will characterize the genetic
networks controlled by Eya1 and Brg1 in the MM progenitor cell development at different stages. This study
will provide a broad view of Eya1-Brg1 association with their targets in Eya1-expressing cells at different
stages during nephron formation and provide a rich source for future discovery of cis-regulatory module-
associated mechanisms. The information can be used to guide nephron repair and regeneration. This study
will provide valuable insights into the genetic networks that underlie congenital nephron deficits.

## Key facts

- **NIH application ID:** 9968233
- **Project number:** 5R01DK064640-17
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** PIN-XIAN XU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $573,034
- **Award type:** 5
- **Project period:** 2003-08-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968233

## Citation

> US National Institutes of Health, RePORTER application 9968233, Transcription factors in early kidney development (5R01DK064640-17). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9968233. Licensed CC0.

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