Intronic promoter drives the BORIS-regulated expression of FerT in colon carcinoma cells.
Fer is an intracellular tyrosine kinase that accumulates in most mammalian tissues. A truncated variant of Fer, FerT, is uniquely detected in spermatogenic cells and is absent from normal somatic tissues. Here, we show that in addition to Fer, FerT also accumulates in CC cells and in metastases derived from colorectal tumors, but not in normal human cells. Thus, FerT is a new member of the CTA protein family. Transcription of the ferT gene in CC cells was found to be driven by an intronic promoter residing in intron 10 of the fer gene and to be regulated by another CTA, the Brother of the Regulator of Imprinted Sites (BORIS) transcription factor. BORIS binds to the ferT promoter and down-regulation of BORIS significantly decreases the expression of ferT in CC cells. Accumulation of the ferT RNA was also regulated by the DNA methylation status and paralleled the expression profile of the boris transcript. Accordingly, the intronic ferT promoter was found to be hypomethylated in cancer cells expressing the FerT protein, by comparison with non-expressers. Collectively, we show here that FerT is a new CTA whose accumulation in CC cells, commonly considered low CTA expressers, is controlled by a novel transcription regulatory mechanism.
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
Adar
A
Makovski
Etai
E
Yaffe
Sally
S
Shpungin
Uri
U
Nir
D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D045325:HCT116 Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics
C456540:CTCFL protein, human; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C052602:proto-oncogene protein c-fes-fps; D011505:Protein-Tyrosine Kinases