Krüppel-like factor 1 is a core cardiomyogenic trigger in zebrafish

Science ◽  
2021 ◽  
Vol 372 (6538) ◽  
pp. 201-205
Author(s):  
Masahito Ogawa ◽  
Fan-Suo Geng ◽  
David T. Humphreys ◽  
Esther Kristianto ◽  
Delicia Z. Sheng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Heart Development ◽  
Transcriptional Regulator ◽  
Cardiac Regeneration ◽  
Epigenetic Reprogramming ◽  
Mitochondrial Metabolism ◽  
Adult Zebrafish ◽  
Transcription Factor Network ◽  
Oxidative Respiration

Cardiac regeneration requires dedifferentiation and proliferation of mature cardiomyocytes, but the mechanisms underlying this plasticity remain unclear. Here, we identify a potent cardiomyogenic role for Krüppel-like factor 1 (Klf1/Eklf), which is induced in adult zebrafish myocardium upon injury. Myocardial inhibition of Klf1 function does not affect heart development, but it severely impairs regeneration. Transient Klf1 activation is sufficient to expand mature myocardium in uninjured hearts. Klf1 directs epigenetic reprogramming of the cardiac transcription factor network, permitting coordinated cardiomyocyte dedifferentiation and proliferation. Myocardial expansion is supported by Klf1-induced rewiring of mitochondrial metabolism from oxidative respiration to anabolic pathways. Our findings establish Klf1 as a core transcriptional regulator of cardiomyocyte renewal in adult zebrafish hearts.

scholarly journals Inhibition of let-7c Regulates Cardiac Regeneration after Cryoinjury in Adult Zebrafish

2019 ◽  
Vol 6 (2) ◽  
pp. 16 ◽  
Author(s):  
Suneeta Narumanchi ◽  
Karri Kalervo ◽  
Sanni Perttunen ◽  
Hong Wang ◽  
Katariina Immonen ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Regeneration ◽  
Nuclear Antigen ◽  
Heart Regeneration ◽  
Adult Zebrafish ◽  
Tissue Samples ◽  
Micro Rnas ◽  
Proliferating Cell ◽  
Zebrafish Heart

The let-7c family of micro-RNAs (miRNAs) is expressed during embryonic development and plays an important role in cell differentiation. We have investigated the role of let-7c in heart regeneration after injury in adult zebrafish. let-7c antagomir or scramble injections were given at one day after cryoinjury (1 dpi). Tissue samples were collected at 7 dpi, 14 dpi and 28 dpi and cardiac function was assessed before cryoinjury, 1 dpi, 7 dpi, 14 dpi and 28 dpi. Inhibition of let-7c increased the rate of fibrinolysis, increased the number of proliferating cell nuclear antigen (PCNA) positive cardiomyocytes at 7 dpi and increased the expression of the epicardial marker raldh2 at 7 dpi. Additionally, cardiac function measured with echocardiography recovered slightly more rapidly after inhibition of let-7c. These results reveal a beneficial role of let-7c inhibition in adult zebrafish heart regeneration.

scholarly journals Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8

2015 ◽  
Vol 36 (6) ◽  
pp. 913-922 ◽  
Author(s):  
Nallani Vijay Kumar ◽  
Jianbo Yang ◽  
Jitesh K. Pillai ◽  
Swati Rawat ◽  
Carlos Solano ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Transcriptional Response ◽  
Transcriptional Regulator ◽  
Yeast Protein ◽  
Content Type ◽  
Arsenic Tolerance ◽  
Arsenic Sensing

The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeastSaccharomyces cerevisiae. However, the mechanism by which Yap8 senses the presence of arsenic and activates transcription of detoxification genes is unknown. Here we demonstrate that Yap8 directly binds to trivalent arsenite [As(III)]in vitroandin vivoand that approximately one As(III) molecule is bound per molecule of Yap8. As(III) is coordinated by three sulfur atoms in purified Yap8, and our genetic and biochemical data identify the cysteine residues that form the binding site as Cys132, Cys137, and Cys274. As(III) binding by Yap8 does not require an additional yeast protein, and Yap8 is regulated neither at the level of localization nor at the level of DNA binding. Instead, our data are consistent with a model in which a DNA-bound form of Yap8 acts directly as an As(III) sensor. Binding of As(III) to Yap8 triggers a conformational change that in turn brings about a transcriptional response. Thus, As(III) binding to Yap8 acts as a molecular switch that converts inactive Yap8 into an active transcriptional regulator. This is the first report to demonstrate how a eukaryotic protein couples arsenic sensing to transcriptional activation.

scholarly journals Transcription factor network downstream of protease activated receptors (PARs) modulating mouse bladder inflammation

2007 ◽  
Vol 8 (1) ◽  
pp. 17 ◽  
Author(s):  
Ricardo Saban ◽  
Cindy Simpson ◽  
Carole A Davis ◽  
Igor Dozmorov ◽  
Julie Maier ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protease Activated Receptors ◽  
Transcription Factor Network ◽  
Bladder Inflammation

Abstract 297: Nkx2–5 Transcriptionally Activates C-kit-ligand And Regulates Cardiac Progenitor Cell Populations

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rebecca L Scotland ◽  
Xiaozhong Shi ◽  
Anwarul Ferdous ◽  
Michael Kyba ◽  
Daniel J Garry
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Progenitor Cell ◽  
Transcriptional Regulator ◽  
Luciferase Reporter ◽  
Transcriptional Networks ◽  
Cell Populations ◽  
Cardiac Progenitor Cell ◽  
Downstream Target ◽  
Kit Ligand

C-kit-ligand, also known as stem cell factor, is expressed broadly and has a functional role during hematopoesis, gametogenesis, melanogenesis, mast cell growth and differentiation. Although the receptor for c-kit-ligand, c-kit, has been utilized as a marker to identify cardiac stem cell and progenitor cell populations, the transcriptional regulation and biological function of c-kit-ligand during cardiogenesis has not been defined. Here we demonstrate that c-kit-ligand is a novel downstream target of Nkx2–5. The homeodomain transcription factor, Nkx2–5, is one of the earliest markers of the cardiac lineage and mice lacking this transcription factor are nonviable. To identify potential Nkx2–5 downstream target genes, we utilized ES/EBs that were engineered to overexpress Nkx2–5 and undertook transcriptome analysis of embyroid bodies with and without Nkx2–5 induction. We observed a significant increase in c-kit-ligand expression following Nkx2–5 induction suggesting a role for Nkx2–5 in the activation of c-kit-ligand. Furthermore, analysis of the c-kit-ligand promoter revealed three evolutionarily conserved Nkx2–5 response elements, supporting the notion that Nkx2–5 is a transcriptional regulator of gene expression. We undertook transcriptional assays and transfected the c-kit-ligand promoter-luciferase reporter in the absence and presence of increasing amounts of Nkx2–5. We observed that Nkx2–5, in a dose dependent fashion, was a potent transcriptional activator of c-kit-ligand. These studies enhance our understanding of Nkx2–5 mediated transcriptional networks and further emphasize that Nkx2–5 is an important transcriptional regulator of cardiac progenitor cell populations.

scholarly journals Cardiac regeneration following cryoinjury in the adult zebrafish targets a maturation-specific biomechanical remodeling program

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Joseph K. Yu ◽  
Padmini Sarathchandra ◽  
Adrian Chester ◽  
Magdi Yacoub ◽  
Thomas Brand ◽  
...  
Keyword(s):  
Cardiac Regeneration ◽  
Adult Zebrafish

A Feedback Loop Between the Liver-Enriched Transcription Factor Network and Mir-122 Controls Hepatocyte Differentiation

2012 ◽  
Vol 142 (1) ◽  
pp. 119-129 ◽  
Author(s):  
Ilaria Laudadio ◽  
Isabelle Manfroid ◽  
Younes Achouri ◽  
Dominic Schmidt ◽  
Michael D. Wilson ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Feedback Loop ◽  
Hepatocyte Differentiation ◽  
Transcription Factor Network

scholarly journals IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF

2005 ◽  
Vol 201 (8) ◽  
pp. 1197-1203 ◽  
Author(s):  
Kazu Kikuchi ◽  
Anne Y. Lai ◽  
Chia-Lin Hsu ◽  
Motonari Kondo
Keyword(s):  
Transcription Factor ◽  
B Cells ◽  
B Cell ◽  
Target Genes ◽  
Cell Development ◽  
B Cell Development ◽  
Receptor Signaling ◽  
Cell Stage ◽  
Transcription Factor Network ◽  
Stage Transition

Cytokine receptor signals have been suggested to stimulate cell differentiation during hemato/lymphopoiesis. Such action, however, has not been clearly demonstrated. Here, we show that adult B cell development in IL-7−/− and IL-7Rα2/− mice is arrested at the pre–pro-B cell stage due to insufficient expression of the B cell–specific transcription factor EBF and its target genes, which form a transcription factor network in determining B lineage specification. EBF expression is restored in IL-7−/− pre–pro-B cells upon IL-7 stimulation or in IL-7Rα−/− pre–pro-B cells by activation of STAT5, a major signaling molecule downstream of the IL-7R signaling pathway. Furthermore, enforced EBF expression partially rescues B cell development in IL-7Rα−/− mice. Thus, IL-7 receptor signaling is a participant in the formation of the transcription factor network during B lymphopoiesis by up-regulating EBF, allowing stage transition from the pre–pro-B to further maturational stages.

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