Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Regulation of Megakaryocytic differentiation in Cell Line Models by Dynamic Combinatorial Interactions of RUNX1 with Its Cooperating Partners

ABSTRACT: Regulation of Megakaryocytic differentiation in Cell Line Models by Dynamic Combinatorial Interactions of RUNX1 with Its Cooperating Partners Examination of RUNX1 binding in K562 cells, before and following TPA induction and CMK cells. Examination of GATA1 and FOS binding and H3K4me1 and H3K27me3 modification levels following TPA induction in K562 cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Ram Jaschek

PROVIDER: E-GEOD-24777 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dynamic combinatorial interactions of RUNX1 and cooperating partners regulates megakaryocytic differentiation in cell line models.

Pencovich Niv N Jaschek Ram R Tanay Amos A Groner Yoram Y

Blood 20101019 1

Specific interactions of transcription factors (TFs) with their targets are crucial for specifying gene expression programs during cell differentiation. How specificity is maintained despite limited selectivity of individual TF-DNA interactions is not fully understood. RUNX1 TF is among the most frequently mutated genes in human leukemia and an important regulator of megakaryopoiesis. We used megakaryocytic cell lines to characterize the network of RUNX1 targets and cooperating TFs in differenti ...[more]

PMID: 20959602

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Project description:Our goal is to find new genes regulated by p21 in human primary cells . To get it we carried out a gene expression profiling in two different models, human myeloid leukemia K562 cells and human keratinocytes both of them with conditional expression of p21. In order to find genes regulated by p21 in human primary cells we carried out a gene expression profiling in human myeloid leukemia K562 cells with conditional expression of p21. We previously described a K562 derivative, termed Kp21-4, that carries a zinc-inducible p21 gene (Munoz-Alonso MJ et at., 2005). We performed a kinetic study to identify the expression peak of p21 in this system. This transient induction of p21 was accompanied by proliferation arrest and an increase in polyploid cells after 48-72 h (Munoz-Alonso MJ et at., 2005). Actually, 6-12 h of p21 induction with ZnSO4 is sufficient to irreversibly trigger proliferation arrest. Therefore, we chose 12 h as the induction time to analyse p21 effects on the transcriptome of these cells, as gene expression changes later on may be indirect due to other phenotypic effects. We next carried out the gene expression profiling of Kp21-4 cells upon p21 induction by ZnSO4. In order to identify genes specifically modulated by p21 we compared with the cell line Kp27-5, which carries a Zn2+-inducible p27 allele (Munoz-Alonso MJ et at., 2005). p27 is a close relative to p21 that also inhibits CDKs and induce cell cycle arrest . Thus, the comparison serves to identify genes specifically regulated by p21 in our analysis. We subtracted the gene expression changes occurring at 72 h in Kp21-4 cells those genes regulated by p27 in the Kp27-5 cells and genes changed by ZnSO4 treatment in parental K562 cells. So, our intention is to identify only genes regulated at short time of induction by p21 and not by p27. In order to confirm these results we studied the p21-dependent repression of mitotic genes in a different cellular system. A dramatic increase in p21 and p27 in Kp21 and Kp27 were demonstrated by RT-qPCR and immunoblot (as we show in the manuscript). We prepared RNA 12 h and 72h after induction with ZnSO4 and performed large-scale expression assay using the Afftymetrix platform. The clustering analysis revealed that p21 provoked the down-regulation of a number genes involved in cell cycle control not shared by cells expressing p27 (as we show in the manuscript). Our goal, has been getting genes regulated more strongly by p21 and not by p27, in cell cycle and itosis. Our result are supported because we have found the same genes in two different models and also we have validated (by RT-qPCR) more than 20 cell cycle and mitotic genes, found in our affymetrix arrays. Also we have found the region of p21 that is sufficient for gene regulation and for one gene we have described as p21 bind to the promoter. Finally, we have discussed in our manuscript how p21 can do this regulation by bioinformatic analysis of p21-target genes. The sucess of this study is describe a new role of p21 as a transcriptional co-repressor in some systems.

Dataset Information

Regulation of Megakaryocytic differentiation in Cell Line Models by Dynamic Combinatorial Interactions of RUNX1 with Its Cooperating Partners

Publications

Dynamic combinatorial interactions of RUNX1 and cooperating partners regulates megakaryocytic differentiation in cell line models.

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