We mapped the transcriptional regulatory circuitry for six master regulators in human hepatocytes using chromatin immunoprecipitation and high-resolution promoter microarrays. The results show that these regulators form a highly interconnected core circuitry, and reveal the local regulatory network motifs created by regulator-gene interactions. Autoregulation was a prominent theme among these regulators. We found that hepatocyte master regulators tend to bind promoter regions combinatorially and that the number of transcription factors bound to a promoter corresponds with observed gene expression. Our studies reveal portions of the core circuitry of human hepatocytes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1681491 | PMC |
| http://dx.doi.org/10.1038/msb4100059 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification of glycogen synthase kinase 3alpha/beta as a host factor required for hepatitis B virus transcription using high-throughput screening.
Hepatology
January 2025
Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan.
Background Aims: Hepatitis B virus (HBV) leads to severe liver diseases, such as cirrhosis and hepatocellular carcinoma. Identification of host factors that regulate HBV replication can provide new therapeutic targets. The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as an HBV entry receptor has enabled the establishment of hepatic cell lines for analyzing HBV infection and propagation.
View Article and Find Full Text PDFB-Type Trimeric Procyanidins Attenuate Nonalcoholic Hepatic Steatosis Through AMPK/mTOR Signaling Pathway in Oleic Acid-Induced HepG2 Cells and High-Fat Diet- Fed Zebrafish.
Plant Foods Hum Nutr
January 2025
Qinghai Provincial Key Laboratory of Tibetan Medicine Research and CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, 810008, P.R. China.
NAFLD is one of the most common and rapidly increasing liver diseases. Procyanidin C1 and procyanidin C2, B-type trimeric procyanidins, show beneficial effects on regulating lipid metabolism. However, the mechanism underlying these effects remain elusive.
View Article and Find Full Text PDFThe metabolic pathway of Deg-AZM and investigations into the contribution of drug metabolizing enzymes and drug transporters in the drug interactions of Deg-AZM, a clinical-stage new transgelin agonist.
Front Pharmacol
January 2025
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
Introduction: Deglycosylated azithromycin (Deg-AZM), a new transgelin agonist with positive therapeutic effects on slow transit constipation, has been approved for clinical trials in 2024. This work investigated the drug metabolism and transport of Deg-AZM to provide research data for further development of Deg-AZM.
Methods: A combination of UPLC-QTOF-MS was used to obtain metabolite spectra of Deg-AZM in plasma, urine, feces and bile.
Motif distribution and DNA methylation underlie distinct Cdx2 binding during development and homeostasis.
Nat Commun
January 2025
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Transcription factors guide tissue development by binding to developmental stage-specific targets and establishing an appropriate enhancer landscape. In turn, DNA and chromatin modifications direct the genomic binding of transcription factors. However, how transcription factors navigate chromatin features to selectively bind a small subset of all the possible genomic target loci remains poorly understood.
View Article and Find Full Text PDFTherapeutic insight into the role of nuclear protein HNF4α in liver carcinogenesis.
Adv Protein Chem Struct Biol
January 2025
Department of Bio-Medical Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India. Electronic address:
Hepatocyte nuclear factor 4-alpha (HNF4α), a well-preserved member of the nuclear receptor superfamily of transcription factors, is found in the liver. It is recognized as a central controller of gene expression specific to the liver and plays a key role in preserving the liver's homeostasis. Irregular expression of HNF4α is increasingly recognized as a crucial factor in the proliferation, cell death, invasiveness, loss of specialized functions, and metastasis of cancer cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!