SMAR1 binds to T(C/G) repeatvand inhibits tumor progression by regulating miR-371-373 cluster
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
SMAR1 binds to T(C/G) repeatvand inhibits tumor progression by regulating miR-371-373 cluster
|
|
| Creator |
Mathai, Jinumary
Mittal, Smriti P K Alam, Aftab Ranade, Payal Mogare, Devraj Patel, Sonal Saxena, Smita Ghorai, Suvankar Kulkarni, Abhijeet P Chattopadhyay, Samit |
|
| Subject |
Cancer Biology and Inflammatory Disorder Division
|
|
| Description |
Chromatin architecture and dynamics are regulated by various histone and non-histone proteins. The
matrix attachment region binding proteins (MARBPs) play a central role in chromatin organization and function through numerous regulatory proteins. In the present study, we demonstrate that nuclear matrix protein SMAR1 orchestrates global gene regulation as determined by massively parallel ChIPsequencing. The study revealed that SMAR1 binds to T(C/G) repeat and targets genes involved in diverse
biological pathways. We observe that SMAR1 binds and targets distinctly different genes based on the
availability of p53. Our data suggest that SMAR1 binds and regulates one of the imperative microRNA clusters in cancer and metastasis, miR-371-373. It negatively regulates miR-371-373 transcription as confirmed by SMAR1 overexpression and knockdown studies. Further, deletion studies indicate that a ~200 bp region in the miR-371-373 promoter is necessary for SMAR1 binding and transcriptional
repression. Recruitment of HDAC1/mSin3A complex by SMAR1, concomitant with alteration of histone marks results in downregulation of the miRNA cluster. The regulation of miR-371-373 by SMAR1 inhibits breast cancer tumorigenesis and metastasis as determined by in vivo experiments. Overall, our study highlights the binding of SMAR1 to T(C/G) repeat and its role in cancer through miR-371-373
|
|
| Date |
2016-09-27
|
|
| Type |
Article
PeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/2565/1/Scientific_Reports__633779.pdf
Mathai, Jinumary and Mittal, Smriti P K and Alam, Aftab and Ranade, Payal and Mogare, Devraj and Patel, Sonal and Saxena, Smita and Ghorai, Suvankar and Kulkarni, Abhijeet P and Chattopadhyay, Samit (2016) SMAR1 binds to T(C/G) repeatvand inhibits tumor progression by regulating miR-371-373 cluster. Scientific Reports, 6 (33779). 01-14. |
|
| Relation |
http://dx.doi.org/10.1038/srep33779
http://www.eprints.iicb.res.in/2565/ |
|