Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation

The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC) terminal differentiation program. The transcription factors specifically regulating terminal differentia...

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Bibliographic Details
Published in:PloS one 2016-12, Vol.11 (12), p.e0167392-e0167392
Main Authors: Bin, Lianghua, Deng, Liehua, Yang, Hengwen, Zhu, Leqing, Wang, Xiao, Edwards, Michael G, Richers, Brittany, Leung, Donald Y M
Format: Article
Language:English
Subjects:
Biology and life sciences
Biopsy
Care and treatment
Cell adhesion
Cell Differentiation - genetics
Ceramide
Differentiation
DNA-Binding Proteins - biosynthesis
Engineering
Epidermis
Epidermis - growth & development
Epidermis - metabolism
Experiments
Forkhead protein
Forkhead Transcription Factors - antagonists & inhibitors
Forkhead Transcription Factors - biosynthesis
Forkhead Transcription Factors - genetics
Gene expression
Gene Expression Regulation, Developmental
Gene Regulatory Networks - genetics
Gene sequencing
Gene Silencing
Genes
Genetic aspects
Genomics
High-Throughput Nucleotide Sequencing
Hospitals
Humans
Immunology
Keratinization
Keratinocytes
Keratinocytes - metabolism
KLF4 protein
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors - biosynthesis
Laboratories
Medicine and Health Sciences
Mutation
Organogenesis - genetics
Pediatrics
Primary Cell Culture
Protein expression
Proteins
Research and analysis methods
Ribonucleic acid
RNA
RNA sequencing
RNA, Small Interfering
Skin
Transcription (Genetics)
Transcription factors
Transcription Factors - biosynthesis
Transcriptional Activation - genetics
Tumor Suppressor Proteins
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Summary:The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC) terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq) profiling approach, we found that forkhead box c 1 (FOXC1) was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0167392