MiR144/451 Expression Is Repressed by RUNX1 During Megakaryopoiesis and Disturbed by RUNX1/ETO

Kohrs, Nicole; Kolodziej, Stephan; Kuvardina, Olga N.; Herglotz, Julia; Yillah, Jasmin; Herkt, Stefanie; Piechatzek, Alexander; Riester, Gabriela Salinas; Lingner, Thomas; Wichmann, Christian; Bönig, Halvard; Seifried, Erhard; Platzbecker, Uwe; Medyouf, Hind; Grez, Manuel; Lausen, Jörn

doi:10.1371/journal.pgen.1005946

Cited by 25 publications

(21 citation statements)

References 89 publications

(121 reference statements)

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“…For example, myc proto‐oncogene (MYC) activates miR‐17/92 cluster by binding to its promoter and influences the expression of several target genes [SIN3 transcription regulator family member B ( SIN3B ), HMG‐box transcription factor 1 ( HBP1 ), and BTG anti‐proliferation factor 1 ( BTG1 )] (Bo et al, ). Downregulation of miR‐17/92 by CCAAT/enhancer binding protein beta (C/EBPβ) and of miR‐144/451 by runt related transcription factor 1 (RUNX1)/ETO fusion protein is reported in differentiating acute myeloid leukemia (AML) cells and megakaryopoiesis, respectively (Kohrs et al, ; Yan et al, ). Single TFs can regulate multiple miRNA clusters and vice versa .…”

Section: Regulation Of Mirna Cluster Expressionmentioning

confidence: 99%

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Clustered miRNAs and their role in biological functions and diseases

et al. 2018

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MicroRNAs (miRNAs) are endogenous, small non-coding RNAs known to regulate expression of protein-coding genes. A large proportion of miRNAs are highly conserved, localized as clusters in the genome, transcribed together from physically adjacent miRNAs and show similar expression profiles. Since a single miRNA can target multiple genes and miRNA clusters contain multiple miRNAs, it is important to understand their regulation, effects and various biological functions. Like protein-coding genes, miRNA clusters are also regulated by genetic and epigenetic events. These clusters can potentially regulate every aspect of cellular function including growth, proliferation, differentiation, development, metabolism, infection, immunity, cell death, organellar biogenesis, messenger signalling, DNA repair and self-renewal, among others. Dysregulation of miRNA clusters leading to altered biological functions is key to the pathogenesis of many diseases including carcinogenesis. Here, we review recent advances in miRNA cluster research and discuss their regulation and biological functions in pathological conditions.

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Section: Regulation Of Mirna Cluster Expressionmentioning

confidence: 99%

“…RISC, RNA induced silencing complex. megakaryopoiesis, respectively (Kohrs et al, 2016;. Single TFs can regulate multiple miRNA clusters and vice versa.…”

Section: Figmentioning

confidence: 99%

Clustered miRNAs and their role in biological functions and diseases

et al. 2018

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“…In this respect, Cβ3 behaves like an erythroid gene. Recently, we reported that the transcription factor RUNX1 is a suppressor of erythroid TAL1 target genes such as KLF1 and the microRNA miR-144/451 [ 15 , 17 ]. Similar to this observation, we found that RUNX1 acts as repressor of the PRKACB Cβ3 isoform.…”

Section: Discussionmentioning

confidence: 99%

“…Knockdown of TAL1, RUNX1 and GATA1 was achieved with shRNAs present in the pGIPZ vector (Open Biosystems) [ 17 ]. The accession numbers of the pGIPZ constructs is given in Supplementary Material .…”

Section: Methodsmentioning

confidence: 99%

“…Considerable progress has been made to better understand the function of TAL1 by the identification of TAL1 target genes [ 12 – 14 ]. Recently, we discovered that TAL1 interacts with RUNX1 (RUNT-related transcription factor 1) on erythroid genes in progenitor cells [ 15 – 17 ]. However, although TAL1 is readily expressed in erythrocyte/megakaryocyte progenitors and in the megakaryocytic lineage [ 18 ], little is known about the function of TAL1 in megakaryocytes.…”

Section: Introductionmentioning

confidence: 99%

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Hematopoietic transcription factors and differential cofactor binding regulatePRKACBisoform expression

et al. 2017

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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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MicroRNAs as regulators and effectors of hematopoietic transcription factors

2019

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Hematopoiesis is a highly-regulated development process orchestrated by lineagespecific transcription factors that direct the generation of all mature blood cells types, including red blood cells, megakaryocytes, granulocytes, monocytes, and lymphocytes. Under homeostatic conditions, the hematopoietic system of the typical adult generates over 10 11 blood cells daily throughout life. In addition, hematopoiesis must be responsive to acute challenges due to blood loss or infection. MicroRNAs (miRs) cooperate with transcription factors to regulate all aspects of hematopoiesis, including stem cell maintenance, lineage selection, cell expansion, and terminal differentiation. Distinct miR expression patterns are associated with specific hematopoietic lineages and stages of differentiation and functional analyses have elucidated essential roles for miRs in regulating cell transitions, lineage selection, maturation, and function. MiRs function as downstream effectors of hematopoietic transcription factors and as upstream regulators to control transcription factor levels. Multiple miRs have been shown to play essential roles. Regulatory networks comprised of differentially expressed lineage-specific miRs and hematopoietic transcription factors are involved in controlling the quiescence and self-renewal of hematopoietic stem cells as well as proliferation and differentiation of lineage-specific progenitor cells during erythropoiesis, myelopoiesis, and lymphopoiesis. This review focuses on hematopoietic miRs that function as upstream regulators of central hematopoietic transcription factors required for normal hematopoiesis.

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MiR144/451 Expression Is Repressed by RUNX1 During Megakaryopoiesis and Disturbed by RUNX1/ETO

Cited by 25 publications

References 89 publications

Clustered miRNAs and their role in biological functions and diseases

Clustered miRNAs and their role in biological functions and diseases

Hematopoietic transcription factors and differential cofactor binding regulatePRKACBisoform expression

MicroRNAs as regulators and effectors of hematopoietic transcription factors

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