Extracellular signals that regulate liver transcription factors during hepatic differentiation in vitro.
Open accessAbstract
A complex cell culture environment has been shown to maintain the differentiated state of hepatocytes, yet the mechanisms by which environmental cues selectively maintain liver-specific gene transcription have been unknown. In this paper we show that the hepatic environment regulates the activities of at least three liver-enriched transcription factors, eE-TF, eG-TF/HNF3, and eH-TF, that activate the mouse serum albumin enhancer. eE-TF is a heat-stable factor that has a DNA-binding specificity similar to that of the liver transcription factor C/EBP, but is a distinct protein. eG-TF/HNF3 contributes to the liver-specific transcription of several other serum protein genes. eH-TF binds to a TGTTTGC sequence that occurs at regulatory sites of the albumin promoter, the hepatitis B virus enhancer, and other hepatic genes. eE-TF, eG-TF/HNF3, and eH-TF are regulated by different combinations of the following cell culture conditions: a hormonally defined serum-free medium; an extracellular matrix gel; and a transformation-competent simian virus 40 large T antigen. We propose a regulatory network model to explain how cues from the cell lineage and the extracellular environment coordinately help maintain the activities of transcription factors involved in hepatocyte differentiation.
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We found substantial overlap between established pioneer factors and methylated-DNA-binding proteins, such as FOXA and GATA families.
“Indeed, we observed a large overlap between known pioneer TFs and proteins that bind to methylated DNA (for example, forkhead box protein A (FOXA) and GATA families, which are the best-studied pioneer factors)106,108–110.”
From Transcription factors as readers and effectors of DNA methylation (2016) · cites this paper as [110]
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- Authors
- Liu, J. K., DiPersio, C. M., & Zaret, K. S.
- Affiliations
- Brown University (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1991-02
- Volume
- 11
- Issue
- 2
- Pages
- 773-784
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC359729
- OpenAlex
- W1797059431
- Cited by
- 168
- References
- 57
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2016: 3 · 2015: 1 · 2012: 1
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chicago Community Trust
- McKnight Foundation
- Searle Scholars Program
- National Institutes of Health
- National Institute of General Medical Sciences (GM 36477)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- hepatocyte differentiation, liver-specific transcription factors, extracellular signals, HNF-3, C/EBP, serum-free medium, extracellular matrix, SV40 large T antigen
- MeSH terms
- Animals, Base Sequence, Blood Proteins, Cell Differentiation, Cell Line, Deoxyribonuclease I, DNA-Binding Proteins, Enhancer Elements, Genetic, Liver, Molecular Sequence Data, Nuclear Proteins, Promoter Regions, Genetic, Serum Albumin, Transcription Factors, Transcription, Genetic, Transfection, Oligonucleotide Probes, Signal Transduction, Mice, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta
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