Transcriptional regulation of bidirectional gene pairs by 17-β-estradiol in MCF-7 breast cancer cells

Abstract

Using cDNA microarray analysis, we previously identified a set of differentially expressed genes in primary breast tumors based on the status of estrogen and progesterone receptors. In the present study, we performed an integrated computer-assisted and manual search of potential estrogen response element (ERE) binding sites in the promoter region of these genes to characterize their potential to be regulated by estrogen receptors (ER). Publicly available databases were used to annotate the position of these genes in the genome and to extract a 5'flanking region 2 kb upstream to 2 kb downstream of the transcription start site for transcription binding site analysis. The search for EREs and other binding sites was performed using several publicly available programs. Overall, approximately 40% of the genes analyzed were potentially able to be regulated by estrogen via ER. In addition, 17% of these genes are located very close to other genes organized in a head-to-head orientation with less than 1.0 kb between their transcript units, sharing a bidirectional promoter, and could be classified as bidirectional gene pairs. Using quantitative real-time PCR, we further investigated the effects of 17β-estradiol and antiestrogens on the expression of the bidirectional gene pairs in MCF-7 breast cancer cells. Our results showed that some of these gene pairs, such as TXNDC9/ EIF5B, GALNS/TRAPPC2L, and SERINC1/PKIB, are modulated by 17β-estradiol via ER in MCF-7 breast cancer cells. Here, we also characterize the promoter region of potential ER-regulated genes and provide new information on the transcriptional regulation of bidirectional gene pairs.

Knockdown of TXNDC9 induces apoptosis and autophagy in glioma and mediates cell differentiation by p53 activation

“…Many members of the Thioredoxin family are mainly involved in the redox reaction of the body. It is highly expressed in many solid tumors such as liver cancer [ 14 ], colon cancer [ 31 ], breast cancer [ 32 ] and so on. Other experiments showed that TXNDC9 was up-regulated in some oxaliplatin-resistant strains.…”

The dual lives of bidirectional promoters

“…In fact, it is well known that methylation of the binding sites for GABPA (which is highly enriched at bidirectional promoters [11]) is inhibited by DNA methylation [34], particularly at the BRCA1 promoter [4,31]. Finally, a very recent report suggests that estrogen controlled genes with estrogen receptor binding sites close to the proximal promoter are over-represented by bidirectional promoters, an observation that merits future exploration [15]. …”

Proteome-Wide Effect of 17-β-Estradiol and Lipoxin A4 in an Endometriotic Epithelial Cell Line

“…eIF5B, reported to be the most catalytically active of the translation initiation factors ( 49 ), was one of the top 25 proteins regulated. Interestingly, this protein was previously demonstrated to be increased by E2 in MCF-7 estrogen-responsive breast cancer cells via ER ( 50 ).…”