# Chromatin architectural protein CTCF and regulation of skin development and tumorigenesis

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $476,469

## Abstract

PROJECT SUMMARY
 The long-term goal of this project is to understand how epithelial stem cells in the skin establish distinct
patterns of gene activation and silencing during their differentiation into specialized cell lineages and how these
genetic programs are re-organized during skin regeneration and tumorigenesis.
 It is now widely accepted that in addition to signaling/transcription factor-mediated mechanisms, lineage-
specific gene expression programs are also regulated epigenetically, i.e., via covalent DNA/histone
modifications, as well as via spatial arrangements of the genes and their enhancer elements in the nucleus.
 Enhancer-promoter interactions serve as key determinants providing functional and structural frameworks
for cell-specific transcription controlled by lineage-specific transcription factors. However, enhancer-promoter
regulatory networks are substantially re-organized during cell transition towards malignancy, which include an
aberrant exposure of gene promoters to inappropriate regulatory elements resulting in activation of pro-
oncogenes, as well as in silencing of the tumor suppressor genes.
 CCCTC-binding factor (CTCF) serves as one of the core architectural proteins that plays a key role in the
control the establishment and maintenance of enhancer/promoter interactions. CTCF gene is frequently mutated
in cancers, and abrogation of its tumor-suppressor activity contributes to cancer development and progression.
 Our preliminary data demonstrate that CTCF is expressed in both mouse and human epidermis, while
Krt14-driven Ctcf genetic ablation results in severe alterations in skin development, epidermal barrier
maintenance, and tumorigenesis. In this multi-PI proposal, we will test a hypothesis that CTCF serves as critical
determinant that control the establishment and maintenance of the enhancer-promoter regulatory networks in
skin epithelial stem cells and their progenies during development and postnatal homeostasis, while alterations
in such networks result in skin tumorigenesis. We will address this hypothesis via two Specific Aims:
 1. Define the roles of CTCF in the establishment and maintenance of lineage-specific higher-order
chromatin structure, enhancer-promoter regulatory networks and gene expression in distinct
populations of skin epithelial cells during development and hair cycle-associated skin regeneration.
 2. Delineate the roles for Ctcf in regulation of gene expression, 3D chromatin organization and
enhancer-promoter interactions in the skin epithelial cells during tumorigenesis.
 This project will have a fundamental impact on our current knowledge of epigenetic mechanisms that
regulate genome reorganization in stem cells during their differentiation and tumorigenesis and will promote the
progress towards the development of novel epigenetic drugs as a new paradigm for treatment of skin disorders.

## Key facts

- **NIH application ID:** 10148640
- **Project number:** 5R01AR071727-05
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** VLADIMIR A BOTCHKAREV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $476,469
- **Award type:** 5
- **Project period:** 2017-02-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10148640

## Citation

> US National Institutes of Health, RePORTER application 10148640, Chromatin architectural protein CTCF and regulation of skin development and tumorigenesis (5R01AR071727-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10148640. Licensed CC0.

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