Hematopoietic transcription factors and differential cofactor binding regulate PRKACB isoform expression
نویسندگان
چکیده
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.
منابع مشابه
Evaluation of MYB93 and MAD8 Genes in Transgenic and Non-Transgenic Rice
Increasing drought tolerance, especially in rice, which is one of the most important crops in Asia, is necessary. Transcription factors are specific sequence DNA-binding proteins that are capable of activating or suppressing transcription. These proteins regulate gene expression levels by binding to cis regulatory elements in the promoter of target genes to control various biological processes ...
متن کاملMycobacterium avium subsp. paratuberculosis induces differential cytosine methylation at miR-21 transcription start site region
Mycobacterium aviumsubspecies paratuberculosis (MAP), as an obligate intracellular bacterium, causes paratuberculosis (Johne’s disease) in ruminants. Plus, MAP has consistently been isolated from Crohn’s disease (CD) lesions in humans; a notion implying possible direct causative ...
متن کاملActivated notch inhibits myogenic activity of the MADS-Box transcription factor myocyte enhancer factor 2C.
Skeletal muscle gene expression is dependent on combinatorial associations between members of the MyoD family of basic helix-loop-helix (bHLH) transcription factors and the myocyte enhancer factor 2 (MEF2) family of MADS-box transcription factors. The transmembrane receptor Notch interferes with the muscle-inducing activity of myogenic bHLH proteins, and it has been suggested that this inhibito...
متن کاملPRKACB is downregulated in non-small cell lung cancer and exogenous PRKACB inhibits proliferation and invasion of LTEP-A2 cells
Protein kinase cAMP-dependent catalytic β (PRKACB) is a member of the Ser/Thr protein kinase family and a key effector of the cAMP/PKA-induced signal transduction involved in numerous cellular process, including cell proliferation, apoptosis, gene transcription, metabolism and differentiation. In the present study, the expression pattern of PRKACB in non-small cell lung cancer (NSCLC) and the e...
متن کاملTranscriptional interactions between the pannier isoforms and the cofactor U-shaped during neural development in Drosophila
The pannier (pnr) gene of Drosophila melanogaster encodes two isoforms that belong to the family of GATA transcription factors. The isoforms share an expression domain in the wing discs where they exhibit distinct functions during regulation of the proneural achaete/scute (ac/sc) genes. We previously identified two regions in the pnr locus that drive reporter expression in transgenic lines in p...
متن کامل