RGD Reference Report - The methyltransferase G9a regulates HoxA9-dependent transcription in AML. - Rat Genome Database

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The methyltransferase G9a regulates HoxA9-dependent transcription in AML.

Authors: Lehnertz, B  Pabst, C  Su, L  Miller, M  Liu, F  Yi, L  Zhang, R  Krosl, J  Yung, E  Kirschner, J  Rosten, P  Underhill, TM  Jin, J  Hebert, J  Sauvageau, G  Humphries, RK  Rossi, FM 
Citation: Lehnertz B, etal., Genes Dev. 2014 Feb 15;28(4):317-27. doi: 10.1101/gad.236794.113.
RGD ID: 9589168
Pubmed: PMID:24532712   (View Abstract at PubMed)
PMCID: PMC3937511   (View Article at PubMed Central)
DOI: DOI:10.1101/gad.236794.113   (Journal Full-text)

Chromatin modulators are emerging as attractive drug targets, given their widespread implication in human cancers and susceptibility to pharmacological inhibition. Here we establish the histone methyltransferase G9a/EHMT2 as a selective regulator of fast proliferating myeloid progenitors with no discernible function in hematopoietic stem cells (HSCs). In mouse models of acute myeloid leukemia (AML), loss of G9a significantly delays disease progression and reduces leukemia stem cell (LSC) frequency. We connect this function of G9a to its methyltransferase activity and its interaction with the leukemogenic transcription factor HoxA9 and provide evidence that primary human AML cells are sensitive to G9A inhibition. Our results highlight a clinical potential of G9A inhibition as a means to counteract the proliferation and self-renewal of AML cells by attenuating HoxA9-dependent transcription.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
acute myeloid leukemia disease_progressionISOEhmt2 (Mus musculus)9589168; 9589168 RGD 
acute myeloid leukemia disease_progressionIMP 9589168 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ehmt2  (euchromatic histone lysine methyltransferase 2)

Genes (Mus musculus)
Ehmt2  (euchromatic histone lysine N-methyltransferase 2)

Genes (Homo sapiens)
EHMT2  (euchromatic histone lysine methyltransferase 2)


Additional Information