RGD Reference Report - Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth. - Rat Genome Database

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Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth.

Authors: Krieg, AJ  Rankin, EB  Chan, D  Razorenova, O  Fernandez, S  Giaccia, AJ 
Citation: Krieg AJ, etal., Mol Cell Biol. 2010 Jan;30(1):344-53. doi: 10.1128/MCB.00444-09. Epub .
RGD ID: 9590225
Pubmed: PMID:19858293   (View Abstract at PubMed)
PMCID: PMC2798291   (View Article at PubMed Central)
DOI: DOI:10.1128/MCB.00444-09   (Journal Full-text)

The hypoxia-inducible transcription factors (HIFs) directly and indirectly mediate cellular adaptation to reduced oxygen tensions. Recent studies have shown that the histone demethylase genes JMJD1A, JMJD2B, and JARID1B are HIF targets, suggesting that HIFs indirectly influence gene expression at the level of histone methylation under hypoxia. In this study, we identify a subset of hypoxia-inducible genes that are dependent on JMJD1A in both renal cell and colon carcinoma cell lines. JMJD1A regulates the expression of adrenomedullin (ADM) and growth and differentiation factor 15 (GDF15) under hypoxia by decreasing promoter histone methylation. In addition, we demonstrate that loss of JMJD1A is sufficient to reduce tumor growth in vivo, demonstrating that histone demethylation plays a significant role in modulating growth within the tumor microenvironment. Thus, hypoxic regulation of JMJD1A acts as a signal amplifier to facilitate hypoxic gene expression, ultimately enhancing tumor growth.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colon cancer severityIMP 9590225human gene in a mouse modelRGD 
colon cancer severityISOKDM3A (Homo sapiens)9590225; 9590225human gene in a mouse modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdm3a  (lysine demethylase 3A)

Genes (Mus musculus)
Kdm3a  (lysine (K)-specific demethylase 3A)

Genes (Homo sapiens)
KDM3A  (lysine demethylase 3A)


Additional Information