# Epigenetic Regulation of region-specific keratin expression patterns

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $526,755

## Abstract

Summary
 The objective is to understand the organizing principles of the skin for future use in regenerative medicine.
Progress has been made toward generating skin progenitor cells. However, before significant progress in
clinical applications can be made, we must know how the skin exhibits region-specific characteristics with
unique functions and architectures. While human skins show regional specificity (scalp, face, palm, etc), mice
do not. Chicken skin does show dramatic regional specificity and is accessible to experimentation, making it an
ideal model for this type of study. Tissue recombination studies showed dermis controls the phenotypes, and
epidermal progenitors respond by making appropriate appendage phenotypes. In this proposal, we will focus
on how regional specific keratinocyte differentiation is controlled by epigenetic processes. Our recent work
showed that chicken β-keratin clusters on Chr25 are organized in five sub-clusters, each enriched in a globally
different skin region (feather, scale, claw, “macro-regional specificity”); whereas the β-keratin clusters on Chr27
are differentially expressed in different within-feather regions (rachis vs barb) or feather generations (downy vs
adult contour feathers) made from stem cells in the same follicle (“micro- regional specificity”). Thus, we
hypothesize there is a hierarchical correspondence between the skin regional topographic map and genomic
organization of b-keratin clusters. Preliminary data of Chr25 keratins show typical enhancers in front of keratin
sub-clusters, while Chr27 keratins surprisingly show 38 peaks of CTCF/KLF4 binding motifs, strongly
suggesting intra-cluster chromatin looping and complex combination potential. In Aim 1, we will use histone
ChIP-Seq to identify how typical enhancer(s) differentially regulate the b-keratin cluster within the EDC in
different skin regions. We will also analyze how intra-cluster higher-order chromatin looping in the Chr27
keratin cluster may lead to differential keratin expression in within-feather differences. Feather and scales at
different competent stages, tissue recombinant explants with reprogrammed epithelial fate, and experimental
conditions in which scales are converted toward feathers, and adult contour feathers converted toward downy
feathers will be used to monitor the epigenetic changes. In Aim 2, we will analyze how the genome organizers
CTCF, KLF4, and SATB1/2 bind DNA and configure chromatin conformation at the keratin loci in the above
conditions. Appendage phenotypes caused by suppression of these genome organizers will be analyzed.

## Key facts

- **NIH application ID:** 10171552
- **Project number:** 5R01AR047364-19
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Cheng-Ming Chuong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $526,755
- **Award type:** 5
- **Project period:** 2002-05-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171552

## Citation

> US National Institutes of Health, RePORTER application 10171552, Epigenetic Regulation of region-specific keratin expression patterns (5R01AR047364-19). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10171552. Licensed CC0.

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