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Absent, small or homeotic 2-like protein (ASH2L) enhances the transcription of the estrogen receptor ? gene through GATA-binding protein 3 (GATA3).

ABSTRACT: ASH2L is a component of MLL complexes that confer H3K4 trimethylation. The ASH2L gene is located at 8q11-12, which is often amplified in breast cancers. We found that increased ASH2L expression, which can result from gene amplification, is often correlated with increased ER? expression in both breast cancer cell lines and primary breast cancers. Forced expression of ASH2L induced ER? expression in mammary epithelial cells, whereas depletion of ASH2L suppressed ER? expression in breast cancer cells. To understand the mechanism by which ASH2L regulates ER? expression, we identified GATA3 as the binding protein of ASH2L. ASH2L was shown to potentiate the transcriptional activity of GATA3. ASH2L was recruited to the enhancer of the ER? gene through GATA3 to promote ER? transcription. This study established that ASH2L enhances ER? expression as a coactivator of GATA3 in breast cancers.

SUBMITTER: Qi J

PROVIDER: S-EPMC4223337 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Absent, small or homeotic 2-like protein (ASH2L) enhances the transcription of the estrogen receptor α gene through GATA-binding protein 3 (GATA3).

Qi Jin J Huo Lei L Zhu Yiwei Tony YT Zhu Yi-Jun YJ

The Journal of biological chemistry 20140925 45

ASH2L is a component of MLL complexes that confer H3K4 trimethylation. The ASH2L gene is located at 8q11-12, which is often amplified in breast cancers. We found that increased ASH2L expression, which can result from gene amplification, is often correlated with increased ERα expression in both breast cancer cell lines and primary breast cancers. Forced expression of ASH2L induced ERα expression in mammary epithelial cells, whereas depletion of ASH2L suppressed ERα expression in breast cancer cel ...[more]

PMID: 25258321

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Project description:BackgroundMice homozygous for the juvenile alopecia mutation (jal) display patches of hair loss that appear as soon as hair develops in the neonatal period and persist throughout life. Although a report initially describing this mouse variant suggested that jal maps to mouse Chromosome 13, our preliminary mapping analysis did not support that claim.ResultsTo map jal to a particular mouse chromosome, we produced a 103-member intraspecific backcross panel that segregated for jal, and typed it for 93 PCR-scorable, microsatellite markers that are located throughout the mouse genome. Only markers from the centromeric tip of Chromosome 2 failed to segregate independently from jal, suggesting that jal resides in that region. To more precisely define jal's location, we characterized a second, 374-member backcross panel for the inheritance of five microsatellite markers from proximal Chromosome 2. This analysis restricted jal's position between D2Mit359 and D2Mit80, an interval that includes Il2ra (for interleukin 2 receptor, alpha chain), a gene that is known to be associated with alopecia areata in humans. Complementation testing with an engineered null allele of Il2ra, however, showed that jal is a mutation in a distinct gene. To further refine the location of jal, the 374-member panel was typed for a set of four single-nucleotide markers located between D2Mit359 and D2Mit80, identifying a 0.55 Mb interval where jal must lie. This span includes ten genes-only one of which, Gata3 (for GATA binding protein 3)-is known to be expressed in skin. Complementation testing between jal and a Gata3 null allele produced doubly heterozygous, phenotypically mutant offspring.ConclusionsThe results presented indicate that the jal mutation is a mutant allele of the Gata3 gene on mouse Chromosome 2. We therefore recommend that the jal designation be changed to Gata3jal, and suggest that this mouse variant may provide an animal model for at least some forms of focal alopecia that have their primary defect in the hair follicle and lack an inflammatory component.

Dataset Information

Absent, small or homeotic 2-like protein (ASH2L) enhances the transcription of the estrogen receptor ? gene through GATA-binding protein 3 (GATA3).

Publications

Absent, small or homeotic 2-like protein (ASH2L) enhances the transcription of the estrogen receptor α gene through GATA-binding protein 3 (GATA3).

Similar Datasets

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