Mode of action of the retrogene product SNAI1P, a SNAIL homolog, in human breast cancer cells
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SNAI1P, a protein coded by a retrogene, is a member of the SNAI family of E2-box binding transcriptional repressors. To evaluate whether the mode of action of SNAI1P is similar to those of the other predominant members of the SNAI family, we studied its action on human claudin 7 (CLDN7) gene promoter which has seven E2-boxes. We over-expressed FLAG-tagged SNAI1P in MCF7 and MDA-MB-468 cells. SNAI1P inhibited the expression of CLDN7 in these recombinant cells. SNAI1P also inhibited cloned CLDN7 gene promoter activity in human breast cancer cells. ChIP assays revealed that SNAI1P is recruited on the CLDN7 gene promoter along with the co-repressor CtBP1 and the effector HDAC1. Treatment of the cells with trichostatin A, an inhibitor of HDAC1, abrogated the repressor activity of SNAI1P. These data suggest that SNAI1P inhibits CLDN7 gene promoter epigenetically in breast cancer cells through chromatin remodeling.
KeywordsSNAI1P SNAIL Claudin 7 E2-box Transcriptional repression CtBP1 HDAC1
C-terminal binding protein 1
Histone deacetylase 1
Protein arginine methyl transferase 1
Histone methyl transferase 1
This work was supported by the DOD-CDMRP IDEA Grant # W81XWH-06-1-0466 to GC. Immunofluorescence analysis was performed in the MMC Morphology Core facility (supported by NIH grants U54NS041071-06, G12RR03032-19, U54CA91408, and U54RR019192-04).
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