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Signal transducer and activator of transcription STAT5 is recruited to c-Myc super-enhancer
Rascle, Anne, Pinz, Sophia and Unser, Samy (2016) Signal transducer and activator of transcription STAT5 is recruited to c-Myc super-enhancer. BMC Molecular Biology 17 (10), pp. 1-11.Date of publication of this fulltext: 28 Jul 2016 15:09
Article
DOI to cite this document: 10.5283/epub.34167
Abstract
Background: c-Myc has been proposed as a putative target gene of signal transducer and activator of transcription 5 (STAT5). No functional STAT5 binding site has been identified so far within the c-Myc gene locus, therefore a direct transcriptional regulation by STAT5 remains uncertain. c-Myc super-enhancer, located 1.7 Mb downstream of the c-Myc gene locus, was recently reported as essential for ...
Background: c-Myc has been proposed as a putative target gene of signal transducer and activator of transcription 5 (STAT5). No functional STAT5 binding site has been identified so far within the c-Myc gene locus, therefore a direct transcriptional regulation by STAT5 remains uncertain. c-Myc super-enhancer, located 1.7 Mb downstream of the c-Myc gene locus, was recently reported as essential for the regulation of c-Myc gene expression by hematopoietic transcription factors and bromodomain and extra-terminal (BET) proteins and for leukemia maintenance. c-Myc super-enhancer is composed of five regulatory regions (E1-E5) which recruit transcription and chromatin-associated factors, mediating chromatin looping and interaction with the c-Myc promoter. Results: We now show that STAT5 strongly binds to c-Myc super-enhancer regions E3 and E4, both in normal and transformed Ba/F3 cells. We also found that the BET protein bromodomain-containing protein 2 (BRD2), a co-factor of STAT5, co-localizes with STAT5 at E3/E4 in Ba/F3 cells transformed by the constitutively active STAT5-1*6 mutant, but not in non-transformed Ba/F3 cells. BRD2 binding at E3/E4 coincides with c-Myc transcriptional activation and is lost upon treatment with deacetylase and BET inhibitors, both of which inhibit STAT5 transcriptional activity and c-Myc gene expression. Conclusions: Our data suggest that constitutive STAT5 binding to c-Myc super-enhancer might contribute to BRD2 maintenance and thus allow sustained expression of c-Myc in Ba/F3 cells transformed by STAT5-1*6.
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| Item type | Article | ||||
| Journal or Publication Title | BMC Molecular Biology | ||||
| Publisher: | BIOMED CENTRAL LTD | ||||
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| Open Access Type: | Gold (with APC) | ||||
| Place of Publication: | LONDON | ||||
| Volume: | 17 | ||||
| Number of Issue or Book Chapter: | 10 | ||||
| Page Range: | pp. 1-11 | ||||
| Date | 14 April 2016 | ||||
| Institutions | Medicine > Lehrstuhl für Immunologie | ||||
| Identification Number |
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| Keywords | HISTONE DEACETYLASE INHIBITOR; LONG-RANGE ENHANCERS; LEUKEMIA-CELLS; IN-VIVO; HEMATOPOIETIC-CELLS; BET BROMODOMAINS; EXPRESSION; IDENTIFICATION; PROLIFERATION; GENE; STAT5; c-Myc; BET; BRD2; Super-enhancer; Chromatin | ||||
| Dewey Decimal Classification | 600 Technology > 610 Medical sciences Medicine | ||||
| Status | Published | ||||
| Refereed | Yes, this version has been refereed | ||||
| Created at the University of Regensburg | Yes | ||||
| URN of the UB Regensburg | urn:nbn:de:bvb:355-epub-341677 | ||||
| Item ID | 34167 |
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