# Regulators of epidermal growth and differentiation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $480,298

## Abstract

Project Summary/Abstract
Background: The prevailing model of epidermal differentiation is that transcription
factors recruit RNA Polymerase II to differentiation gene promoters only upon the
induction of differentiation. It is possible that mechanisms downstream of transcription
initiation such as transcriptional elongation can have major impacts on regulating
epidermal growth and differentiation. We have shown that specific elongation factors
such as ELL and ELL2 are necessary for epidermal growth while SPT6 is essential for
differentiation through the control of transcription elongation.
Objective/hypothesis: This proposal seeks to understand the regulation of epidermal
stem and progenitor cell self-renewal and differentiation through transcription elongation.
We have found that up to 30% of induced epidermal differentiation genes contain
promoter proximal paused RNA polymerase II in stem and progenitor cells. Upon
differentiation, specific elongation factors such as SPT6 are necessary to promote the
transcriptional elongation of these paused differentiation genes. In stem and progenitor
cells there are also elongation factors that promote the transcription of growth and
proliferation genes to allow for epidermal renewal.
Specific Aims: (1) The role of transcription elongation factors on epidermal growth and
differentiation (2) Mechanisms on how elongation factors control epidermal growth and
differentiation.
Study Design: To study epidermal homeostasis in a more clinically relevant setting, we
generate 3-dimensionally intact human skin, containing human epidermal cells (that
have been permanently knocked down for transcription elongation factors) in the context
of human dermal stroma and basement membrane, regenerated on immune
compromised mice. By using this model, we can perform loss of function experiments on
the transcription elongation factors in regenerated human skin to characterize their role
in epidermal growth and differentiation. We will also use chromatin immunoprecipitations
followed by next generation sequencing to determine which genes the elongation factors
bind and regulate.

## Key facts

- **NIH application ID:** 10294731
- **Project number:** 2R01AR066530-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** GEORGE L SEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $480,298
- **Award type:** 2
- **Project period:** 2015-02-17 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294731

## Citation

> US National Institutes of Health, RePORTER application 10294731, Regulators of epidermal growth and differentiation (2R01AR066530-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10294731. Licensed CC0.

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