Hematopoietic transcription factors and differential cofactor binding regulate PRKACB isoform expression

Hematopoietic differentiation is controlled by key transcription factors, which regulate stem cell functions and differentiation. TAL1 is a central transcription factor for hematopoietic stem cell development in the embr
Hematopoietic differentiation is controlled by key transcription factors, which regulate stem cell functions and differentiation. TAL1 is a central transcription factor for hematopoietic stem cell development in the embryo and for gene regulation during erythroid/megakaryocytic differentiation. Knowledge of the target genes controlled by a given transcription factor is important to understand its contribution to normal development and disease. To uncover direct target genes of TAL1 we used high affinity streptavidin/biotin-based chromatin precipitation (Strep-CP) followed by Strep-CP on ChIP analysis using ChIP promoter arrays. We identified 451 TAL1 target genes in K562 cells. Furthermore, we analysed the regulation of one of these genes, the catalytic subunit beta of protein kinase A (PRKACB), during megakaryopoiesis of K562 and primary human CD34+ stem cell/progenitor cells. We found that TAL1 together with hematopoietic transcription factors RUNX1 and GATA1 binds to the promoter of the isoform 3 of PRKACB (Cβ3). During megakaryocytic differentiation a coactivator complex on the Cβ3 promoter, which includes WDR5 and p300, is replaced with a corepressor complex. In this manner, activating chromatin modifications are removed and expression of the PRKACB-Cβ3 isoform during megakaryocytic differentiation is reduced. Our data uncover a role of the TAL1 complex in controlling differential isoform expression of PRKACB. These results reveal a novel function of TAL1, RUNX1 and GATA1 in the transcriptional control of protein kinase A activity, with implications for cellular signalling control during differentiation and disease.
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Metadaten
Author:Olga Nikolaevna Lausen, Stefanie Herkt, Annekarin Meyer, Lucas Schneider, Jasmin Yillah, Nicole Kohrs, Halvard-Björn Bönig, Erhard Seifried, Carsten Müller-Tidow, Jörn Lausen
URN:urn:nbn:de:hebis:30:3-431646
DOI:http://dx.doi.org/10.18632/oncotarget.17386
ISSN:1949-2553
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=29069738
Parent Title (English):OncoTarget
Publisher:Impact Journals LLC
Place of publication:[s. l.]
Document Type:Article
Language:English
Date of Publication (online):2017/05/18
Date of first Publication:2017/04/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/05/22
Tag:epigenetics; gene regulation; hematopoiesis; oncogenes; transcription factors
Volume:8
Pagenumber:14
First Page:1
Last Page:14
Note:
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
HeBIS PPN:421385081
Institutes:Biowissenschaften
Medizin
Georg-Speyer-Haus
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Medizin
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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