Abstract
The FOXF1 (Forkhead box F1) gene, located on chromosome 16q24.1 encodes a member of the FOX family of transcription factors characterized by a distinct forkhead DNA binding domain. FOXF1 plays an important role in epithelium-mesenchyme signaling, as a downstream target of Sonic hedgehog pathway. Heterozygous point mutations and genomic deletions involving FOXF1 have been reported in newborns with a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV). In addition, genomic deletions upstream to FOXF1 identified in ACDMPV patients have revealed that FOXF1 expression is tightly regulated by distal tissue-specific enhancers. Interestingly, FOXF1 has been found to be incompletely paternally imprinted in human lungs; characterized genomic deletions arose de novo exclusively on maternal chromosome 16, with most of them being Alu-Alu mediated. Regulation of FOXF1 expression likely utilizes a combination of chromosomal looping, differential methylation of an upstream CpG island overlapping GLI transcription factor binding sites, and the function of lung-specific long non-coding RNAs (lncRNAs). Foxf1 knock-out mouse models demonstrated its critical role in mesoderm differentiation and in the development of pulmonary vasculature. Additionally, epigenetic inactivation of FOXF1 has been reported in breast and colorectal cancers, whereas overexpression of FOXF1 has been associated with a number of other human cancers, e.g. medulloblastoma and rhabdomyosarcoma. Constitutional duplications of FOXF1 have recently been reported in congenital intestinal malformations. Thus, understanding the genomic and epigenetic complexity at the FOXF1 locus will improve diagnosis, prognosis, and treatment of ACDMPV and other human disorders associated with FOXF1 alterations.
Keywords: ACDMPV, Gene regulation, Genomic-imprinting, Long non-coding RNA, Lung development, Pulmonary vasculature.
Current Genomics
Title:Genomic and Epigenetic Complexity of the FOXF1 Locus in 16q24.1: Implications for Development and Disease
Volume: 16 Issue: 2
Author(s): Avinash V. Dharmadhikari, Przemyslaw Szafranski, Vladimir V. Kalinichenko and Pawel Stankiewicz
Affiliation:
Keywords: ACDMPV, Gene regulation, Genomic-imprinting, Long non-coding RNA, Lung development, Pulmonary vasculature.
Abstract: The FOXF1 (Forkhead box F1) gene, located on chromosome 16q24.1 encodes a member of the FOX family of transcription factors characterized by a distinct forkhead DNA binding domain. FOXF1 plays an important role in epithelium-mesenchyme signaling, as a downstream target of Sonic hedgehog pathway. Heterozygous point mutations and genomic deletions involving FOXF1 have been reported in newborns with a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV). In addition, genomic deletions upstream to FOXF1 identified in ACDMPV patients have revealed that FOXF1 expression is tightly regulated by distal tissue-specific enhancers. Interestingly, FOXF1 has been found to be incompletely paternally imprinted in human lungs; characterized genomic deletions arose de novo exclusively on maternal chromosome 16, with most of them being Alu-Alu mediated. Regulation of FOXF1 expression likely utilizes a combination of chromosomal looping, differential methylation of an upstream CpG island overlapping GLI transcription factor binding sites, and the function of lung-specific long non-coding RNAs (lncRNAs). Foxf1 knock-out mouse models demonstrated its critical role in mesoderm differentiation and in the development of pulmonary vasculature. Additionally, epigenetic inactivation of FOXF1 has been reported in breast and colorectal cancers, whereas overexpression of FOXF1 has been associated with a number of other human cancers, e.g. medulloblastoma and rhabdomyosarcoma. Constitutional duplications of FOXF1 have recently been reported in congenital intestinal malformations. Thus, understanding the genomic and epigenetic complexity at the FOXF1 locus will improve diagnosis, prognosis, and treatment of ACDMPV and other human disorders associated with FOXF1 alterations.
Export Options
About this article
Cite this article as:
Dharmadhikari Avinash V., Szafranski Przemyslaw, V. Kalinichenko Vladimir and Stankiewicz Pawel, Genomic and Epigenetic Complexity of the FOXF1 Locus in 16q24.1: Implications for Development and Disease, Current Genomics 2015; 16 (2) . https://dx.doi.org/10.2174/1389202916666150122223252
DOI https://dx.doi.org/10.2174/1389202916666150122223252 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Current Genomics in Cardiovascular Research
Cardiovascular diseases are the main cause of death in the world, in recent years we have had important advances in the interaction between cardiovascular disease and genomics. In this Research Topic, we intend for researchers to present their results with a focus on basic, translational and clinical investigations associated with ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Immune Responses to Fungal Infections and Therapeutic Implications
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Polo-Like Kinase 1 as a Potential Therapeutic Target for Osteosarcoma
Current Pharmaceutical Design SNew Trends in the Development of Opioid Peptide Analogues as Advanced Remedies for Pain Relief
Current Topics in Medicinal Chemistry Editorial [Hot Topic: Benefits, Problems and Alternatives to COX-2 Inhibition (Guest Editor: Angel Lanas)]
Current Topics in Medicinal Chemistry COX Selectivity and Animal Models for Colon Cancer
Current Pharmaceutical Design Procathepsin D as a Tumor Marker, Anti-Cancer Drug or Screening Agent
Anti-Cancer Agents in Medicinal Chemistry Potential Beneficial Effects of Garlic in Oncohematology
Mini-Reviews in Medicinal Chemistry Targeting the Human Thioredoxin System by Diverse Strategies to Treat Cancer and Other Pathologies
Recent Patents on DNA & Gene Sequences Bone Morphogenetic Proteins and its Receptors; Therapeutic Targets in Cancer Progression and Bone Metastasis?
Current Pharmaceutical Design Monoclonal Antibodies in Solid Tumours
Current Clinical Pharmacology Role of PPAR in Cardiovascular Diseases
Recent Patents on Cardiovascular Drug Discovery Damnacanthal: A Promising Compound as a Medicinal Anthraquinone
Anti-Cancer Agents in Medicinal Chemistry Will Antiangiogenic Agents be a Future for Mesothelioma Therapy?
Current Medicinal Chemistry Synthesis and Evaluation of A New Series of Thiazole Derivatives as Potential Antitumor Agents and MMP Inhibitors
Anti-Cancer Agents in Medicinal Chemistry The Molecular Mechanisms of TRAIL Resistance in Cancer Cells: Help in Designing New Drugs
Current Pharmaceutical Design Molecular Docking Studies of Glycyrrhetinic Acid Derivatives as Anti- Colorectal Cancer Agents
Current Computer-Aided Drug Design In Vitro Collapsing Colon Cancer Cells by Selectivity of Disulfiram-Loaded Charge Switchable Nanoparticles Against Cancer Stem Cells
Recent Patents on Anti-Cancer Drug Discovery Natural Product-Inspired Synthesis of Thiazolidine and Thiazolidinone Compounds and their Anticancer Activities
Current Pharmaceutical Design Natural Products to Improve Quality of Life Targeting for Colon Drug Delivery
Current Drug Delivery Glycoconjugates of Quinolines: Application in Medicinal Chemistry
Mini-Reviews in Medicinal Chemistry