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PMID:24265704

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Citation

Zhang, C, Hong, Z, Ma, W, Ma, D, Qian, Y, Xie, W, Tie, F and Fang, M (2013) Drosophila UTX coordinates with p53 to regulate ku80 expression in response to DNA damage. PLoS ONE 8:e78652

Abstract

UTX is known as a general factor that activates gene transcription during development. Here, we demonstrate an additional essential role of UTX in the DNA damage response, in which it upregulates the expression of ku80 in Drosophila, both in cultured cells and in third instar larvae. We further showed that UTX mediates the expression of ku80 by the demethylation of H3K27me3 at the ku80 promoter upon exposure to ionizing radiation (IR) in a p53-dependent manner. UTX interacts physically with p53, and both UTX and p53 are recruited to the ku80 promoter following IR exposure in an interdependent manner. In contrast, the loss of utx has little impact on the expression of ku70, mre11, hid and reaper, suggesting the specific regulation of ku80 expression by UTX. Thus, our findings further elucidate the molecular function of UTX.

Links

PubMed PMC3827076 Online version:10.1371/journal.pone.0078652

Keywords

Animals; Antigens, Nuclear/genetics; Base Sequence; Cell Survival/genetics; Cell Survival/radiation effects; DNA Damage; DNA Repair/genetics; DNA Repair/radiation effects; DNA-Binding Proteins/genetics; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/cytology; Drosophila melanogaster/genetics; Drosophila melanogaster/metabolism; Drosophila melanogaster/radiation effects; Gene Expression Regulation/genetics; Gene Expression Regulation/radiation effects; Histones/metabolism; Methylation/radiation effects; Oxidoreductases, N-Demethylating/genetics; Oxidoreductases, N-Demethylating/metabolism; Promoter Regions, Genetic/genetics; Promoter Regions, Genetic/radiation effects; Tumor Suppressor Protein p53/metabolism; Up-Regulation/genetics; Up-Regulation/radiation effects

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:Q8MSM8

involved_in

GO:0071480: cellular response to gamma radiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9NGX6

involved_in

GO:0071480: cellular response to gamma radiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VL07

involved_in

GO:0071557: histone H3-K27 demethylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VL07

enables

GO:0071558: histone demethylase activity (H3-K27 specific)

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q9VL07

enables

GO:1990841: promoter-specific chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q9VL07

involved_in

GO:0071480: cellular response to gamma radiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VL07

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VL07

involved_in

GO:1990248: regulation of transcription from RNA polymerase II promoter in response to DNA damage

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:HID

involved_in

GO:0071480: cellular response to gamma radiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:RPR

involved_in

GO:0071480: cellular response to gamma radiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8IMZ4

enables

GO:1990841: promoter-specific chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q8IMZ4

involved_in

GO:0071480: cellular response to gamma radiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8IMZ4

involved_in

GO:1990248: regulation of transcription from RNA polymerase II promoter in response to DNA damage

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q8IMZ4

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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