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Rascle, Anne ; Pinz, Sophia ; Unser, Samy

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
Artikel
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.



Beteiligte Einrichtungen


Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftBMC Molecular Biology
Verlag:BIOMED CENTRAL LTD
Ort der Veröffentlichung:LONDON
Band:17
Nummer des Zeitschriftenheftes oder des Kapitels:10
Seitenbereich:S. 1-11
Datum14 April 2016
InstitutionenMedizin > Lehrstuhl für Immunologie
Identifikationsnummer
WertTyp
10.1186/s12867-016-0063-yDOI
Stichwörter / KeywordsHISTONE 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-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenJa
URN der UB Regensburgurn:nbn:de:bvb:355-epub-341677
Dokumenten-ID34167

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