scholarly journals Lysine-Specific Demethylase 2 Suppresses Lipid Influx and Metabolism in Hepatic Cells

2015 ◽  
Vol 35 (7) ◽  
pp. 1068-1080 ◽  
Author(s):  
Katsuya Nagaoka ◽  
Shinjiro Hino ◽  
Akihisa Sakamoto ◽  
Kotaro Anan ◽  
Ryuta Takase ◽  
...  
Keyword(s):  
Cell Damage ◽  
Cellular Processes ◽  
Metabolic Plasticity ◽  
Hepatic Cells ◽  
Lysine Specific Demethylase ◽  
Metabolic Remodeling ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Lipid Metabolism Gene ◽  
Histone H3k4 ◽  
Factor C

Cells link environmental fluctuations, such as nutrition, to metabolic remodeling. Epigenetic factors are thought to be involved in such cellular processes, but the molecular basis remains unclear. Here we report that the lysine-specific demethylase 2 (LSD2) suppresses the flux and metabolism of lipids to maintain the energy balance in hepatic cells. Using transcriptome and chromatin immunoprecipitation-sequencing analyses, we revealed that LSD2 represses the genes involved in lipid influx and metabolism through demethylation of histone H3K4. Selective recruitment of LSD2 at lipid metabolism gene loci was mediated in part by a stress-responsive transcription factor, c-Jun. Intriguingly, LSD2 depletion increased the intracellular levels of many lipid metabolites, which was accompanied by an increased susceptibility to toxic cell damage in response to fatty acid exposure. Our data demonstrate that LSD2 maintains metabolic plasticity under fluctuating environment in hepatocytes by mediating the cross talk between the epigenome and metabolism.

scholarly journals LSD1 defines erythroleukemia metabolism by controlling the lineage-specific transcription factors GATA1 and C/EBPα

2021 ◽  
Vol 5 (9) ◽  
pp. 2305-2318
Author(s):  
Kensaku Kohrogi ◽  
Shinjiro Hino ◽  
Akihisa Sakamoto ◽  
Kotaro Anan ◽  
Ryuta Takase ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Target Genes ◽  
Aerobic Glycolysis ◽  
Clinical Samples ◽  
Gene Encoding ◽  
Heme Synthesis ◽  
Metabolic Remodeling ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Factor C

Abstract Acute myeloid leukemia (AML) is a heterogenous malignancy characterized by distinct lineage subtypes and various genetic/epigenetic alterations. As with other neoplasms, AML cells have well-known aerobic glycolysis, but metabolic variations depending on cellular lineages also exist. Lysine-specific demethylase-1 (LSD1) has been reported to be crucial for human leukemogenesis, which is currently one of the emerging therapeutic targets. However, metabolic roles of LSD1 and lineage-dependent factors remain to be elucidated in AML cells. Here, we show that LSD1 directs a hematopoietic lineage-specific metabolic program in AML subtypes. Erythroid leukemia (EL) cells particularly showed activated glycolysis and high expression of LSD1 in both AML cell lines and clinical samples. Transcriptome, chromatin immunoprecipitation–sequencing, and metabolomic analyses revealed that LSD1 was essential not only for glycolysis but also for heme synthesis, the most characteristic metabolic pathway of erythroid origin. Notably, LSD1 stabilized the erythroid transcription factor GATA1, which directly enhanced the expression of glycolysis and heme synthesis genes. In contrast, LSD1 epigenetically downregulated the granulo-monocytic transcription factor C/EBPα. Thus, the use of LSD1 knockdown or chemical inhibitor dominated C/EBPα instead of GATA1 in EL cells, resulting in metabolic shifts and growth arrest. Furthermore, GATA1 suppressed the gene encoding C/EBPα that then acted as a repressor of GATA1 target genes. Collectively, we conclude that LSD1 shapes metabolic phenotypes in EL cells by balancing these lineage-specific transcription factors and that LSD1 inhibitors pharmacologically cause lineage-dependent metabolic remodeling.

scholarly journals Interplay of BAF and MLL4 promotes cell type-specific enhancer activation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Young-Kwon Park ◽  
Ji-Eun Lee ◽  
Zhijiang Yan ◽  
Kaitlin McKernan ◽  
Tommy O’Haren ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Chromatin Remodeling ◽  
Direct Evidence ◽  
Cell Type ◽  
Chromatin Regulators ◽  
Chromatin Remodeling Complex ◽  
Histone H3k4 ◽  
Cell Type Specific ◽  
Pioneer Transcription Factor ◽  
Factor C

AbstractCell type-specific enhancers are activated by coordinated actions of lineage-determining transcription factors (LDTFs) and chromatin regulators. The SWI/SNF chromatin remodeling complex BAF and the histone H3K4 methyltransferase MLL4 (KMT2D) are both implicated in enhancer activation. However, the interplay between BAF and MLL4 in enhancer activation remains unclear. Using adipogenesis as a model system, we identify BAF as the major SWI/SNF complex that colocalizes with MLL4 and LDTFs on active enhancers and is required for cell differentiation. In contrast, the promoter enriched SWI/SNF complex PBAF is dispensable for adipogenesis. By depleting BAF subunits SMARCA4 (BRG1) and SMARCB1 (SNF5) as well as MLL4 in cells, we show that BAF and MLL4 reciprocally regulate each other’s binding on active enhancers before and during adipogenesis. By focusing on enhancer activation by the adipogenic pioneer transcription factor C/EBPβ without inducing cell differentiation, we provide direct evidence for an interdependent relationship between BAF and MLL4 in activating cell type-specific enhancers. Together, these findings reveal a positive feedback between BAF and MLL4 in promoting LDTF-dependent activation of cell type-specific enhancers.

scholarly journals Opportunities for Persistent Luminescent Nanoparticles in Luminescence Imaging of Biological Systems and Photodynamic Therapy

Nanomaterials ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 2015 ◽  
Author(s):  
Douglas L. Fritzen ◽  
Luidgi Giordano ◽  
Lucas C. V. Rodrigues ◽  
Jorge H. S. K. Monteiro
Keyword(s):  
Photodynamic Therapy ◽  
Light Exposure ◽  
Cell Damage ◽  
Biological Systems ◽  
Continuous Light ◽  
Synthetic Methods ◽  
Luminescent Materials ◽  
Future Directions ◽  
Luminescence Imaging ◽  
Cellular Processes

The use of luminescence in biological systems allows us to diagnose diseases and understand cellular processes. Persistent luminescent materials have emerged as an attractive system for application in luminescence imaging of biological systems; the afterglow emission grants background-free luminescence imaging, there is no need for continuous excitation to avoid tissue and cell damage due to the continuous light exposure, and they also circumvent the depth penetration issue caused by excitation in the UV-Vis. This review aims to provide a background in luminescence imaging of biological systems, persistent luminescence, and synthetic methods for obtaining persistent luminescent materials, and discuss selected examples of recent literature on the applications of persistent luminescent materials in luminescence imaging of biological systems and photodynamic therapy. Finally, the challenges and future directions, pointing to the development of compounds capable of executing multiple functions and light in regions where tissues and cells have low absorption, will be discussed.

scholarly journals Metabolic Plasticity in Dendritic Cell Responses: Implications in Allergic Asthma

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Amarjit Mishra
Keyword(s):  
Airway Inflammation ◽  
Lymphocyte Function ◽  
Dc Functions ◽  
Novel Treatments ◽  
Cellular Processes ◽  
Metabolic Plasticity ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Current Review ◽  
Signaling Process

Dendritic cells (DCs) are highly specialized in antigen presentation and play a pivotal role in the initiation, progression, and perpetuation of adaptive immune responses. Emerging immune pathways are being recognized increasingly for DCs and their subsets that differentially regulate T lymphocyte function based on the type and interactions with the antigen. However, these interactions not only alter the signaling process and DC function but also render metabolic plasticity. The current review focuses on the metabolic cues of DCs that coordinate DC activation and differentiation and discuss whether targeting these fundamental cellular processes have implications to control airway inflammation and adaptive immunity. Therefore, strategies using metabolism-based therapeutic manipulation of DC functions could be developed into novel treatments for airway inflammation and asthma.

Effect of lipid peroxidation conditions on calcium-dependent activity of phosphodiesterase 3′,5′-cAMP in the rat brain

Biologia ◽  
2006 ◽  
Vol 61 (6) ◽  
Author(s):  
Monika Ďurfinová ◽  
Marta Brechtlová ◽  
Branislav Líška ◽  
Želmíra Barošková
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Rat Brain ◽  
Cell Damage ◽  
Intracellular Camp ◽  
Calcium Dependent ◽  
Cellular Processes ◽  
Phosphodiesterase 3 ◽  
Higher Temperature ◽  
The Impact

Abstract3′,5′-cAMP plays an important role as a second messenger molecule controlling multiple cellular processes in the brain. Its levels are decreased by phosphodiesterases (PDEs), responsible for hydrolysis of intracellular cAMP. A part of the PDE activity is dependent on the effect of calcium, mediated by its binding to calmodulin. During oxidative stress, precisely these changes in calcium concentration are responsible for cell damage. We have examined the effects of oxidative stress conditions on the activity of PDE in rat brain homogenates. We found a different influence of activated lipid peroxidation conditions (Fe2+ with ascorbate and increased temperature) on the calcium-dependent and calcium-independent PDE activity. The inhibition of Ca2+-dependent PDE was observed, while Ca2+-independent PDE was not influenced. We assume that it might be the impact of lipid peroxidation products or any mechanism activated by the higher temperature on the interaction of the Ca2+-dependent isoform of PDE with the complex calcium-calmodulin. Another explanation might be that the formation of the functioning calcium-calmodulin complex is impossible in these conditions.

scholarly journals Two distinct signalling cascades target the NF-κB regulatory factor c-IAP1 for degradation

2009 ◽  
Vol 420 (1) ◽  
pp. 83-91 ◽  
Author(s):  
Rebecca A. Csomos ◽  
Casey W. Wright ◽  
Stefanie Galbán ◽  
Karolyn A. Oetjen ◽  
Colin S. Duckett
Keyword(s):  
Large Cell ◽  
Nuclear Factor Κb ◽  
Negative Regulator ◽  
Tumour Necrosis Factor Receptor ◽  
Physiological Mechanisms ◽  
Cellular Processes ◽  
Signalling Cascades ◽  
New Gene ◽  
Factor C ◽  
Necrosis Factor

c-IAP1 (cellular inhibitor of apoptosis 1) has recently emerged as a negative regulator of the non-canonical NF-κB (nuclear factor κB) signalling cascade. Whereas synthetic IAP inhibitors have been shown to trigger the autoubiquitination and degradation of c-IAP1, less is known about the physiological mechanisms by which c-IAP1 stability is regulated. In the present paper, we describe two distinct cellular processes that lead to the targeted loss of c-IAP1. Recruitment of a TRAF2 (tumour necrosis factor receptor-associated factor 2)–c-IAP1 complex to the cytoplasmic domain of the Hodgkin's/anaplastic large-cell lymphoma-associated receptor, CD30, leads to the targeting and degradation of the TRAF2–c-IAP1 heterodimer through a mechanism requiring the RING (really interesting new gene) domain of TRAF2, but not c-IAP1. In contrast, the induced autoubiquitination of c-IAP1 by IAP antagonists causes the selective loss of c-IAP1, but not TRAF2, thereby releasing TRAF2. Thus c-IAP1 can be targeted for degradation by two distinct processes, revealing the critical importance of this molecule as a regulator of numerous intracellular signalling cascades.

Transcription factors YY1, Sp1 and Sp3 modulate dystrophin Dp71 gene expression in hepatic cells

2016 ◽  
Vol 473 (13) ◽  
pp. 1967-1976 ◽  
Author(s):  
Katia Peñuelas-Urquides ◽  
Carolina Becerril-Esquivel ◽  
Laura C. Mendoza-de-León ◽  
Beatriz Silva-Ramírez ◽  
José Dávila-Velderrain ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Promoter Region ◽  
Site Directed Mutagenesis ◽  
Cellular Processes ◽  
Specificity Protein 1 ◽  
Hepatic Cells ◽  
Dna Elements ◽  
Yin And Yang ◽  
Specificity Protein ◽  
Flanking Regions

Dystrophin Dp71, the smallest product encoded by the Duchenne muscular dystrophy gene, is ubiquitously expressed in all non-muscle cells. Although Dp71 is involved in various cellular processes, the mechanisms underlying its expression have been little studied. In hepatic cells, Dp71 expression is down-regulated by the xenobiotic β-naphthoflavone. However, the effectors of this regulation remain unknown. In the present study we aimed at identifying DNA elements and transcription factors involved in Dp71 expression in hepatic cells. Relevant DNA elements on the Dp71 promoter were identified by comparing Dp71 5′-end flanking regions between species. The functionality of these elements was demonstrated by site-directed mutagenesis. Using EMSAs and ChIP, we showed that the Sp1 (specificity protein 1), Sp3 (specificity protein 3) and YY1 (Yin and Yang 1) transcription factors bind to the Dp71 promoter region. Knockdown of Sp1, Sp3 and YY1 in hepatic cells increased endogenous Dp71 expression, but reduced Dp71 promoter activity. In summary, Dp71 expression in hepatic cells is carried out, in part, by YY1-, Sp1- and Sp3-mediated transcription from the Dp71 promoter.

scholarly journals Two Arabidopsis Homologs of Human Lysine-Specific Demethylase Function in Epigenetic Regulation of Plant Defense Responses

2021 ◽  
Vol 12 ◽  
Author(s):  
Seong Woo Noh ◽  
Ri-Ra Seo ◽  
Hee Jin Park ◽  
Ho Won Jung
Keyword(s):  
Pseudomonas Syringae ◽  
Epigenetic Regulation ◽  
Plant Immunity ◽  
Systemic Disease ◽  
Defense Responses ◽  
Plant Defense Responses ◽  
Promoter Regions ◽  
Lysine Specific Demethylase ◽  
Genome Wide ◽  
Histone H3k4

Epigenetic marks such as covalent histone modification and DNA methylation are crucial for mitotically and meiotically inherited cellular memory-based plant immunity. However, the roles of individual players in the epigenetic regulation of plant immunity are not fully understood. Here we reveal the functions of two Arabidopsis thaliana homologs of human lysine-specific demethylase1-like1, LDL1 and LDL2, in the maintenance of methyl groups at lysine 4 of histone H3 and in plant immunity to Pseudomonas syringae infection. The growth of virulent P. syringae strains was reduced in ldl1 and ldl2 single mutants compared to wild-type plants. Local and systemic disease resistance responses, which coincided with the rapid, robust transcription of defense-related genes, were more stably expressed in ldl1 ldl2 double mutants than in the single mutants. At the nucleosome level, mono-methylated histone H3K4 accumulated in ldl1 ldl2 plants genome-wide and in the mainly promoter regions of the defense-related genes examined in this study. Furthermore, in silico comparative analysis of RNA-sequencing and chromatin immunoprecipitation data suggested that several WRKY transcription factors, e.g., WRKY22/40/70, might be partly responsible for the enhanced immunity of ldl1 ldl2. These findings suggest that LDL1 and LDL2 control the transcriptional sensitivity of a group of defense-related genes to establish a primed defense response in Arabidopsis.

scholarly journals Structural Characterization of Transcription Factor C/EBPbeta

2014 ◽  
Vol 70 (a1) ◽  
pp. C1510-C1510
Author(s):  
Maria Miller
Keyword(s):  
Dna Binding ◽  
Biological Activities ◽  
Structural Basis ◽  
X Ray Crystallography ◽  
Cellular Processes ◽  
Disordered Protein ◽  
Eukaryotic Genes ◽  
Factor C ◽  
Structural Insights

The basic region:leucine zipper (bZIP) DNA-binding protein, C/EBPbeta, plays a central role in many vital cellular processes, but is also implicated in tumorigenesis, tumor progression, as well as viral replication within cells. C/EBPbeta binds to specific DNA sites as homo- or hetero-dimers and interacts with other transcription factors to control the transcription of a number of eukaryotic genes. C/EBPbeta is an intrinsically repressed protein that is activated in response to growth factors. This study employs a variety of techniques such as sequence analysis, molecular modeling, X-ray crystallography, and mutagenesis to provide structural insights into the mechanisms that modulate the biological activities of C/EBPbeta. Analysis of the primary structure indicates that C/EBPbeta is a largely disordered protein that consists of unstructured regions that have the potential to fold upon binding to molecular partners as well as regions that retain irregular conformations regardless of their environment. Here, a model of the auto-inhibited form of C/EBPbeta is presented as well as the structural basis of its specific dimerization, DNA-binding, and interactions with the p300 transcriptional co-activator.

scholarly journals The transcription factor c-Fos coordinates with histone lysine-specific demethylase 2A to activate the expression of cyclooxygenase-2

Oncotarget ◽  
2015 ◽  
Vol 6 (33) ◽  
pp. 34704-34717 ◽  
Author(s):  
Shaoli Lu ◽  
Yang Yang ◽  
Yipeng Du ◽  
Lin-lin Cao ◽  
Meiting Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cyclooxygenase 2 ◽  
Histone Lysine ◽  
Lysine Specific Demethylase ◽  
Factor C
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