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| Status |
Public on Dec 22, 2010 |
| Title |
Genome-wide maps of HNF4a and HNF4g binding state in HepG2 cells. |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Hepatocyte nuclear factor-4α (HNF4α, NR2A1) is a nuclear receptor which has a critical role in hepatocyte differentiation and the maintenance of homeostasis in the adult liver. However, a detailed understanding of native HNF4α in the steady state remains to be elucidated. Here we report the native HNF4α isoforms, phosphorylation status and complexes in the steady state, as shown by shotgun proteomics in HepG2 hepatocarcinoma cells. Shotgun proteomic analysis revealed the complexity of native HNF4α, including multiple phosphorylation sites and inter-isoform heterodimerization. The associating complexes identified by label-free semi-quantitative proteomic analysis include the following: the DNA-dependent protein kinase catalytic subunit, histone acetyltransferase complexes, mRNA splicing complex, other nuclear receptor coactivator complexes, the chromatin remodeling complex, and the nucleosome remodeling and histone deacetylation complex. Among the associating proteins, GRB10 interacting GYF protein 2 (GIGYF2, PERQ2) is a new candidate cofactor in metabolic regulation. Moreover, an unexpected heterodimerization of HNF4α and Hepatocyte nuclear factor-4γ was found. A biochemical and genome-wide analysis of transcriptional regulation showed that this heterodimerization activates gene transcription. The genes thus transcribed include the cell death-inducing DEF45-like effector b (CIDEB) gene, which is an important regulator of lipid metabolism in the liver. This suggests that the analysis of the distinctive stoichiometric balance of native HNF4α and its cofactor complexes described here is important for an accurate understanding of transcriptional regulation.
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| Overall design |
Examination of HNF4alpha binding sites with domain-specific antibodies and HNF4gamma binding sites in HepG2 cell.
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| Contributor(s) |
Daigo K, Kawamura T, Ohta Y, Ohashi R, Katayose S, Tanaka T, Aburatani H, Naito M, Kodama T, Ihara S, Hamakubo T |
| Citation(s) |
21047794 |
| Submission date |
Nov 12, 2009 |
| Last update date |
May 15, 2019 |
| Contact name |
Kenji Daigo |
| E-mail(s) |
daigo@lsbm.org
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| Phone |
+81-3-5452-5236
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| Fax |
+81-3-5452-5236
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| Organization name |
University of Tokyo
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| Department |
Research Center for Advanced Science and Technology
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| Lab |
Departments of Molecular Biology and Medicine
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| Street address |
#35 4-6-1 Komaba
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| City |
Meguro |
| State/province |
Tokyo |
| ZIP/Postal code |
153-8904 |
| Country |
Japan |
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| Platforms (1) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE18990 |
Proteomic analysis of native hepatocyte nuclear factor-4{alpha} (HNF4{alpha}) isoforms, phosphorylation status, and interactive cofactors. |
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| Relations |
| SRA |
SRP002191 |
| BioProject |
PRJNA123731 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE18989_RAW.tar |
9.9 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Processed data provided as supplementary file |
| Raw data are available in SRA |
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