# Genomic and epigenomic investigations of the transcriptional regulatory network of skin keratinocytes in defined genetic models

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $350,900

## Abstract

PROJECT SUMMARY
 The development and differentiation of the skin epidermis is an important area of research since altered
keratinocyte function is an underlying cause for various skin conditions including inflammatory skin diseases,
cancer and wound healing defects. The transcriptional and epigenetic mechanisms that control development
and differentiation of keratinocytes is not well understood, particularly in the in vivo context of the skin. Hence
our long-term goal is to examine the chromatin state of keratinocytes and identify and characterize the crucial
transcription factors that function as important regulators of epidermal differentiation in health and disease. It is
well established that the transcription factor ΔNp63 plays a critical role in morphogenesis and differentiation of
the skin epidermis, particularly during embryogenesis. However, our current knowledge of the governing
principles by which ΔNp63 interacts with and shapes the chromatin and transcriptional regulatory environment
of keratinocytes is quite limited and based on data amassed primarily from keratinocytes grown in cell culture.
Furthermore, if and how ΔNp63 plays a role in maintaining adult skin homeostasis after the matured epidermis
is formed, has not been adequately addressed due to lack of targeted genetic systems. To address these
knowledge gaps, we have generated well-defined ΔNp63 transgenic and knockout mouse models that allow us
to isolate a pure population of basal-enriched ΔNp63+ve keratinocytes, and to perform robust, inducible deletion
of ΔNp63 in adult tissues. We will leverage the power of emerging genomics and epigenomics toolbox and our
newly developed mouse models to address two important questions. To examine the pioneering function of
ΔNp63, in Aim 1, we will perform ATAC-seq and ChIP-seq experiments and compare the chromatin
architecture of embryonic basal keratinocytes of ΔNp63-null keratinocytes to their wildtype counterparts. We
will also identify ΔNp63 targets in vivo and integrate epigenomic and transcriptomic datasets to better
understand the ΔNp63-dependent gene regulatory mechanisms that are important for embryonic epidermal
maturation. In Aim 2, we will generate ΔNp63 conditional knockouts and examine how loss of ΔNp63 affects
the cellular and molecular dynamics of the maintenance and homeostasis program of the adult skin epidermis.
Furthermore, we will characterize the ΔNp63-governed transcriptional control mechanisms and signaling
pathways in adult skin and identify the molecular mechanisms of the skin phenotype encumbered by loss of
ΔNp63. Collectively, these experiments will shed light on fundamental transcriptional mechanisms of gene
regulation and specifically identify keratinocyte-specific regulatory networks on a broad and dynamic scale.
Long term, such information has clinical and therapeutic implications for human patients who suffer from
disfiguring and debilitating skin diseases resulting from defective keratinocyte differentia...

## Key facts

- **NIH application ID:** 9841379
- **Project number:** 5R01AR073226-03
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** SATRAJIT SINHA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $350,900
- **Award type:** 5
- **Project period:** 2018-03-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841379

## Citation

> US National Institutes of Health, RePORTER application 9841379, Genomic and epigenomic investigations of the transcriptional regulatory network of skin keratinocytes in defined genetic models (5R01AR073226-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9841379. Licensed CC0.

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