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Signal transducer and activator of transcription STAT5 is recruited to c-Myc super-enhancer
Rascle, Anne, Pinz, Sophia und Unser, Samy (2016) Signal transducer and activator of transcription STAT5 is recruited to c-Myc super-enhancer. BMC Molecular Biology 17 (10), S. 1-11.Veröffentlichungsdatum dieses Volltextes: 28 Jul 2016 15:09
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DOI zum Zitieren dieses Dokuments: 10.5283/epub.34167
Zusammenfassung
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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| Dokumentenart | Artikel | ||||
| Titel eines Journals oder einer Zeitschrift | BMC Molecular Biology | ||||
| Verlag: | BIOMED CENTRAL LTD | ||||
|---|---|---|---|---|---|
| Ort der Veröffentlichung: | LONDON | ||||
| Band: | 17 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 10 | ||||
| Seitenbereich: | S. 1-11 | ||||
| Datum | 14 April 2016 | ||||
| Institutionen | Medizin > Lehrstuhl für Immunologie | ||||
| Identifikationsnummer |
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| Stichwörter / 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-Dezimal-Klassifikation | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status | Veröffentlicht | ||||
| Begutachtet | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden | Ja | ||||
| URN der UB Regensburg | urn:nbn:de:bvb:355-epub-341677 | ||||
| Dokumenten-ID | 34167 |
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