RGD Reference Report - Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression. - Rat Genome Database

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Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression.

Authors: Luo, W  Chang, R  Zhong, J  Pandey, A  Semenza, GL 
Citation: Luo W, etal., Proc Natl Acad Sci U S A. 2012 Dec 4;109(49):E3367-76. doi: 10.1073/pnas.1217394109. Epub 2012 Nov 5.
RGD ID: 9587482
Pubmed: PMID:23129632   (View Abstract at PubMed)
PMCID: PMC3523832   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.1217394109   (Journal Full-text)

Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding proteins that play key roles in breast cancer biology. We hypothesized that interaction of HIF-1 with epigenetic regulators may increase HIF-1 transcriptional activity, and thereby promote breast cancer progression. We report that the histone demethylase jumonji domain containing protein 2C (JMJD2C) selectively interacts with HIF-1alpha, but not HIF-2alpha, and that HIF-1alpha mediates recruitment of JMJD2C to the hypoxia response elements of HIF-1 target genes. JMJD2C decreases trimethylation of histone H3 at lysine 9, and enhances HIF-1 binding to hypoxia response elements, thereby activating transcription of BNIP3, LDHA, PDK1, and SLC2A1, which encode proteins that are required for metabolic reprogramming, as well as LOXL2 and L1CAM, which encode proteins that are required for lung metastasis. JMJD2C expression is significantly associated with expression of GLUT1, LDHA, PDK1, LOX, LOXL2, and L1CAM mRNA in human breast cancer biopsies. JMJD2C knockdown inhibits breast tumor growth and spontaneous metastasis to the lungs of mice following mammary fat pad injection. Taken together, these findings establish an important epigenetic mechanism that stimulates HIF-1-mediated transactivation of genes encoding proteins involved in metabolic reprogramming and lung metastasis in breast cancer.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KDM4CHumanBreast Neoplasms  IMP human gene in a mouse modelRGD 
Kdm4cRatBreast Neoplasms  ISOKDM4C (Homo sapiens)human gene in a mouse modelRGD 
Kdm4cMouseBreast Neoplasms  ISOKDM4C (Homo sapiens)human gene in a mouse modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdm4c  (lysine demethylase 4C)

Genes (Mus musculus)
Kdm4c  (lysine (K)-specific demethylase 4C)

Genes (Homo sapiens)
KDM4C  (lysine demethylase 4C)


Additional Information