کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5510928 | 1539371 | 2017 | 15 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Transcriptional consequences of XPA disruption in human cell lines Transcriptional consequences of XPA disruption in human cell lines](/preview/png/5510928.png)
- The dependence of transcription on XPA was determined in human cell lines.
- Of â¼14,000 genes, XPA influenced transcription of only 27 genes by > 1.5-fold.
- The most significant were the steroid hormone metabolism genes AKR1C1 and AKR1C2.
- The results may help explain some defects in xeroderma pigmentosum.
- XPA is confined to the cell nucleus even in the absence of external DNA damage.
Nucleotide excision repair (NER) in mammalian cells requires the xeroderma pigmentosum group A protein (XPA) as a core factor. Remarkably, XPA and other NER proteins have been detected by chromatin immunoprecipitation at some active promoters, and NER deficiency is reported to influence the activated transcription of selected genes. However, the global influence of XPA on transcription in human cells has not been determined. We analyzed the human transcriptome by RNA sequencing (RNA-Seq). We first confirmed that XPA is confined to the cell nucleus even in the absence of external DNA damage, in contrast to previous reports that XPA is normally resident in the cytoplasm and is imported following DNA damage. We then analyzed four genetically matched human cell line pairs deficient or proficient in XPA. Of the â¼14,000 genes transcribed in each cell line, 325 genes (2%) had a significant XPA-dependent directional change in gene expression that was common to all four pairs (with a false discovery rate of 0.05). These genes were enriched in pathways for the maintenance of mitochondria. Only 27 common genes were different by more than 1.5-fold. The most significant hits were AKR1C1 and AKR1C2, involved in steroid hormone metabolism. AKR1C2 protein was lower in all of the immortalized XPA-deficient cells. Retinoic acid treatment led to modest XPA-dependent activation of some genes with transcription-related functions. We conclude that XPA status does not globally influence human gene transcription. However, XPA significantly influences expression of a small subset of genes important for mitochondrial functions and steroid hormone metabolism. The results may help explain defects in neurological function and sterility in individuals with xeroderma pigmentosum.
Journal: DNA Repair - Volume 57, September 2017, Pages 76-90