For the Mouse gene set with the same name, see OHGUCHI_LIVER_HNF4A_TARGETS_DN

Systematic name M2194
Brief description Genes down-regulated in liver samples of liver-specific knockout of HNF4A [GeneID=3172].
Full description or abstract Type 1 iodothyronine deiodinase (Dio1), a selenoenzyme catalyzing the bioactivation of thyroid hormone, is highly expressed in the liver. Dio1 mRNA and enzyme activity levels are markedly reduced in the livers of hepatocyte nuclear factor 4alpha (HNF4alpha)-null mice, thus accounting for its liver-specific expression. Consistent with this deficiency, serum T4 and rT3 concentrations are elevated in these mice compared with those in HNF4alpha-floxed control littermates; however, serum T3 levels are unchanged. Promoter analysis of the mouse Dio1 gene demonstrated that HNF4alpha plays a key role in the transactivation of the mouse Dio1 gene. Deletion and substitution mutation analyses demonstrated that a proximal HNF4alpha site (direct repeat 1 [TGGACAAAGGTGC]; HNF4alpha-RE) is crucial for transactivation of the mouse Dio1 gene by HNF4alpha. Mouse Dio1 is also stimulated by thyroid hormone signaling, but a direct role for thyroid hormone receptor action has not been reported. We also showed that thyroid hormone-inducible Krüppel-like factor 9 (KLF9) stimulates the mouse Dio1 promoter very efficiently through two CACCC sequences that are located on either side of HNF4alpha-RE. Furthermore, KLF9 functions together with HNF4alpha and GATA4 to synergistically activate the mouse Dio1 promoter, suggesting that Dio1 is regulated by thyroid hormone in the mouse through an indirect mechanism requiring prior KLF9 induction. In addition, we showed that physical interactions between the C-terminal zinc finger domain (Cf) of GATA4 and activation function 2 of HNF4alpha and between the basic domain adjacent to Cf of GATA4 and a C-terminal domain of KLF9 are both required for this synergistic response. Taken together, these results suggest that HNF4alpha regulates thyroid hormone homeostasis through transcriptional regulation of the mouse Dio1 gene with GATA4 and KLF9.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18426912   Authors: Ohguchi H,Tanaka T,Uchida A,Magoori K,Kudo H,Kim I,Daigo K,Sakakibara I,Okamura M,Harigae H,Sasaki T,Osborne TF,Gonzalez FJ,Hamakubo T,Kodama T,Sakai J
Exact source Table 2S
Related gene sets (show 1 additional gene sets from the source publication)

(show 26 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform or
identifier namespace
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 171 genes
Gene families ? Categorize these 171 genes by gene family
Show members (show 256 source identifiers mapped to 171 genes)
Version history 3.1: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.