title: Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation.
abstract: 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.
authors.affiliation: The First Affiliated Hospital, Biomedical Translational Research Institute, the International Immunology Center and the Key Laboratory of Antibody Engineering of Guangdong Province, Jinan University, Guangzhou, Guangdong Province, China.|Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America.
authors.forename: Lianghua
authors.identifier: http://orcid.org/0000-0002-3786-0106
authors.initials: L
authors.lastname: Bin
authors.affiliation: The First Affiliated Hospital, Biomedical Translational Research Institute, the International Immunology Center and the Key Laboratory of Antibody Engineering of Guangdong Province, Jinan University, Guangzhou, Guangdong Province, China.
authors.forename: Liehua
authors.initials: L
authors.lastname: Deng
authors.affiliation: The First Affiliated Hospital, Biomedical Translational Research Institute, the International Immunology Center and the Key Laboratory of Antibody Engineering of Guangdong Province, Jinan University, Guangzhou, Guangdong Province, China.
authors.forename: Hengwen
authors.initials: H
authors.lastname: Yang
authors.affiliation: The First Affiliated Hospital, Biomedical Translational Research Institute, the International Immunology Center and the Key Laboratory of Antibody Engineering of Guangdong Province, Jinan University, Guangzhou, Guangdong Province, China.
authors.forename: Leqing
authors.initials: L
authors.lastname: Zhu
authors.affiliation: The First Affiliated Hospital, Biomedical Translational Research Institute, the International Immunology Center and the Key Laboratory of Antibody Engineering of Guangdong Province, Jinan University, Guangzhou, Guangdong Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, Aurora, CO, United States of America.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Edwards
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America.
authors.forename: Brittany
authors.initials: B
authors.lastname: Richers
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America.|Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The State Key Clinical Specialty in Allergy, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Donald Y M
authors.initials: DY
authors.lastname: Leung
mesh_terms: D001706:Biopsy; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004817:Epidermis / Q000254:growth & development / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000235:genetics; D020868:Gene Silencing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis; D038081:Organogenesis / Q000235:genetics; D061251:Primary Cell Culture; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000096:biosynthesis; D015533:Transcriptional Activation / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; C473143:GRHL3 protein, human; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C570799:ZNF750 protein, human