PDX1, säätelee haiman kehitystä, insuliinin promoottorifaktori 1 (APF1) ja moduloi maksasolugeenejä

https://en.wikipedia.org/wiki/PDX1
PDX1 (Pancreatic and Duodenal homeoboX 1), also known as Insulin Promoter Factor 1 (IPF1), is a transcription factor necessary for pancreatic development, including β-cell maturation, and duodenal differentiation. In humans this protein is encoded by the PDX1 gene, which was formerly known as IPF1.

 PubMed haku PDX1Gene

Also known as

GSF; IPF1; IUF1; IDX-1; MODY4; PDX-1; STF-1; PAGEN1

Summary

The protein encoded by this gene is a transcriptional activator of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide (iAPP), and glucose transporter type 2. 

The encoded nuclear protein is involved in the early development of the pancreas and plays a major role in glucose-dependent regulation of insulin gene expression.

 Defects in this gene are a cause of pancreatic agenesis, which can lead to early-onset insulin-dependent diabetes mellitus (IDDM), as well as maturity onset diabetes of the young type 4 (MODY4).

 [provided by RefSeq, Aug 2017]

Expression

Biased expression in duodenum (RPKM 9.6), stomach (RPKM 1.5) and 3 other tissues See more

1. Dependence of expression of regulatory master genes of embryonic development in pancreatic cancer cells on the intracellular concentration of the master regulator PDX1. Kondratyeva LG, et al. Dokl Biochem Biophys, 2017 Jul. PMID 28864896
2. Mild electrical stimulation with heat shock guides differentiation of embryonic stem cells into Pdx1-expressing cells within the definitive endoderm. Koga T, et al. BMC Biotechnol, 2017 Feb 15. PMID 28202025, Free PMC Article
3. Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma. Zhou G, et al. Curr Mol Med, 2016. PMID 26695692, Free PMC Article
4. Adult Human Biliary Tree Stem Cells Differentiate to β-Pancreatic Islet Cells by Treatment with a Recombinant Human Pdx1 Peptide.  
5.   Finally, Pdx1-induced islet-like structures exhibited glucose-regulated C-peptide secretion. In conclusion, the human Pdx1 is highly effective in triggering hBTSC (human biliary tree stem cells ) differentiation toward functional β-pancreatic cells.
6. Cardinale V, et al. PLoS One, 2015. PMID 26252949, Free PMC Article
7. PDX1 binds and represses hepatic genes to ensure robust pancreatic commitment in differentiating human embryonic stem cells. Teo AK, et al. Stem Cell Reports, 2015 Apr 14. PMID 25843046, Free PMC Article, Abstract
   Inactivation of the Pancreatic and Duodenal Homeobox 1 (PDX1) gene causes pancreatic agenesis, which places PDX1 high atop the regulatory network controlling development of this indispensable organ. However, little is known about the identity of PDX1 transcriptional targets.
    We simulated pancreatic development by differentiating human embryonic stem cells (hESCs) into early pancreatic progenitors and subjected this cell population to PDX1 chromatin immunoprecipitation sequencing (ChIP-seq). We identified more than 350 genes bound by PDX1, whose expression was upregulated on day 17 of differentiation. This group included known PDX1 targets and many genes not previously linked to pancreatic development.
    ChIP-seq also revealed PDX1 occupancy at hepatic genes. We hypothesized that simultaneous PDX1-driven activation of pancreatic and repression of hepatic programs underlie early divergence between pancreas and liver. In HepG2 cells and differentiating hESCs, we found that PDX1 binds and suppresses expression of endogenous liver genes. These findings re-brand PDX1 as a context-dependent transcriptional repressor and activator within the same cell type.

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