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7 results on '"Taracha-Wisniewska A"'

1. Vitamin D Receptor Regulates the Expression of the Grainyhead-Like 1 Gene.

Author

Taracha-Wisniewska, Agnieszka, Parks, Emma G. C., Miller, Michal, Lipinska-Zubrycka, Lidia, Dworkin, Sebastian, and Wilanowski, Tomasz

Subjects
*VITAMIN D receptors, *GENE expression, *VITAMIN D, *ORGANS (Anatomy), *CELL physiology, *REPORTER genes, *IMMUNOPRECIPITATION
Abstract

Vitamin D plays an important pleiotropic role in maintaining global homeostasis of the human body. Its functions go far beyond skeletal health, playing a crucial role in a plethora of cellular functions, as well as in extraskeletal health, ensuring the proper functioning of multiple human organs, including the skin. Genes from the Grainyhead-like (GRHL) family code for transcription factors necessary for the development and maintenance of various epithelia. Even though they are involved in many processes regulated by vitamin D, a direct link between vitamin D-mediated cellular pathways and GRHL genes has never been described. We employed various bioinformatic methods, quantitative real-time PCR, chromatin immunoprecipitation, reporter gene assays, and calcitriol treatments to investigate this issue. We report that the vitamin D receptor (VDR) binds to a regulatory region of the Grainyhead-like 1 (GRHL1) gene and regulates its expression. Ectopic expression of VDR and treatment with calcitriol alters the expression of the GRHL1 gene. The evidence presented here indicates a role of VDR in the regulation of expression of GRHL1 and correspondingly a role of GRHL1 in mediating the actions of vitamin D. [ABSTRACT FROM AUTHOR]

Published
2024
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2. Transcription factors Krüppel-like factor 4 and paired box 5 regulate the expression of the Grainyhead-like genes.

Author

Grzegorz Kotarba, Agnieszka Taracha-Wisniewska, Michal Miller, Michal Dabrowski, and Tomasz Wilanowski

Subjects
Medicine, Science
Abstract

Genes from the Grainyhead-like (GRHL) family code for transcription factors necessary for the development and maintenance of various epithelia. These genes are also very important in the development of many types of cancer. However, little is known about the regulation of expression of GRHL genes. Previously, there were no systematic analyses of the promoters of GRHL genes or transcription factors that bind to these promoters. Here we report that the Krüppel-like factor 4 (KLF4) and the paired box 5 factor (PAX5) bind to the regulatory regions of the GRHL genes and regulate their expression. Ectopic expression of KLF4 or PAX5 alters the expression of GRHL genes. In KLF4-overexpressing HEK293 cells, the expression of GRHL1 and GRHL3 genes was upregulated by 32% and 60%, respectively, whereas the mRNA level of GRHL2 gene was lowered by 28% when compared to the respective controls. The levels of GRHL1 and GRHL3 expression were decreased by 30% or 33% in PAX5-overexpressing HEK293 cells. The presence of minor frequency allele of single nucleotide polymorphism rs115898376 in the promoter of the GRHL1 gene affected the binding of KLF4 to this site. The evidence presented here suggests an important role of KLF4 and PAX5 in the regulation of expression of GRHL1-3 genes.

Published
2021
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4. Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types

Author

Sebastian Dworkin, Grzegorz Kotarba, Tomasz Wilanowski, and Agnieszka Taracha-Wisniewska

Subjects
0301 basic medicine, Male, Review, lcsh:Chemistry, Prostate cancer, 0302 clinical medicine, Neoplasms, subcellular localization, Induced pluripotent stem cell, lcsh:QH301-705.5, transcription factor, Spectroscopy, Tissue homeostasis, Uncategorized, General Medicine, hepatocellular carcinoma, prostate cancer, KLF4, Computer Science Applications, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, embryonic structures, Female, Kruppel-Like Transcription Factors, colorectal cancer, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Kruppel-Like Factor 4, breast cancer, stomatognathic system, medicine, Humans, Physical and Theoretical Chemistry, Molecular Biology, Transcription factor, Tumor microenvironment, gastric cancer, Organic Chemistry, Alternative splicing, medicine.disease, microenvironment, lung cancer, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Tumor progression, Cancer research, sense organs
Abstract

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Krüppel-like factor 4 (KLF4) is a transcription factor highly conserved in evolution. It is particularly well known for its role in inducing pluripotent stem cells. In addition, KLF4 plays many roles in cancer. The results of most studies suggest that KLF4 is a tumor suppressor. However, the functioning of KLF4 is regulated at many levels. These include regulation of transcription, alternative splicing, miRNA, post-translational modifications, subcellular localization, protein stability and interactions with other molecules. Simple experiments aimed at assaying transcript levels or protein levels fail to address this complexity and thus may deliver misleading results. Tumor subtypes are also important; for example, in prostate cancer KLF4 is highly expressed in indolent tumors where it impedes tumor progression, while it is absent from aggressive prostate tumors. KLF4 is important in regulating response to many known drugs, and it also plays a role in tumor microenvironment. More and more information is available about upstream regulators, downstream targets and signaling pathways associated with the involvement of KLF4 in cancer. Furthermore, KLF4 performs critical function in the overall regulation of tissue homeostasis, cellular integrity, and progression towards malignancy. Here we summarize and analyze the latest findings concerning this fascinating transcription factor.

Published
2020

7. Transcription factors Krüppel-like factor 4 and paired box 5 regulate the expression of the Grainyhead-like genes

Author

Tomasz Wilanowski, Michal Miller, Michal Dabrowski, Grzegorz Kotarba, and Agnieszka Taracha-Wisniewska

Subjects
Single Nucleotide Polymorphisms, Gene Expression, Electrophoretic Mobility Shift Assay, Biochemistry, Binding Analysis, Mice, Gene Frequency, Gene expression, Regulation of gene expression, Multidisciplinary, Transcriptional Control, Enzymes, Cell biology, Regulatory sequence, Medicine, Oxidoreductases, Luciferase, Research Article, Chromatin Immunoprecipitation, Science, DNA transcription, Kruppel-Like Transcription Factors, Biology, Research and Analysis Methods, Real-Time Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Kruppel-Like Factor 4, DNA-binding proteins, Genetics, Animals, Humans, Gene Regulation, Computer Simulation, Transcription factor, Gene, Chemical Characterization, PAX5 Transcription Factor, Biology and Life Sciences, Proteins, Promoter, Regulatory Proteins, Repressor Proteins, HEK293 Cells, Gene Expression Regulation, Enzymology, Ectopic expression, Chromatin immunoprecipitation, Transcription Factors
Abstract

Genes from the Grainyhead-like (GRHL) family code for transcription factors necessary for the development and maintenance of various epithelia. These genes are also very important in the development of many types of cancer. However, little is known about the regulation of expression of GRHL genes. Previously, there were no systematic analyses of the promoters of GRHL genes or transcription factors that bind to these promoters. Here we report that the Krüppel-like factor 4 (KLF4) and the paired box 5 factor (PAX5) bind to the regulatory regions of the GRHL genes and regulate their expression. Ectopic expression of KLF4 or PAX5 alters the expression of GRHL genes. In KLF4-overexpressing HEK293 cells, the expression of GRHL1 and GRHL3 genes was upregulated by 32% and 60%, respectively, whereas the mRNA level of GRHL2 gene was lowered by 28% when compared to the respective controls. The levels of GRHL1 and GRHL3 expression were decreased by 30% or 33% in PAX5-overexpressing HEK293 cells. The presence of minor frequency allele of single nucleotide polymorphism rs115898376 in the promoter of the GRHL1 gene affected the binding of KLF4 to this site. The evidence presented here suggests an important role of KLF4 and PAX5 in the regulation of expression of GRHL1-3 genes.

Published
2021
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