scholarly journals TET1-DNA Hydroxymethylation Mediated Oligodendrocyte Homeostasis is Required for CNS Myelination and Remyelination

2019 ◽  
Author(s):  
Ming Zhang ◽  
Jian Wang ◽  
Kaixiang Zhang ◽  
Guozhen Lu ◽  
Keke Ren ◽  
...  
Keyword(s):  
Target Genes ◽  
Calcium Release ◽  
System Development ◽  
Nervous System Development ◽  
Oligodendrocyte Differentiation ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Dna Hydroxymethylation ◽  
Adult Mice ◽  
A Genome

AbstractTen-eleven translocation (TET) proteins, encoding dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role in oligodendrocyte homeostasis, myelination and remyelination remains elusive. Here, we detected a genome-wide and locus-specific DNA hydroxymethylation landscape shift during oligodendrocyte-progenitor (OPC) differentiation. Ablation of Tet1, but not Tet3, results in stage-dependent defects in oligodendrocyte development and myelination in the brain. The mice lacking Tet1 in the oligodendrocyte lineage develop schizophrenia-like behaviors. We further show that TET1 is also required for proper remyelination after demyelination injury in the adult mice. Transcriptomic and DNA hydroxymethylation profiling revealed a critical TET1-regulated epigenetic program for oligodendrocyte differentiation and identified a set of TET1-5hmC target genes associated with myelination, cell division, and calcium transport. Tet1-deficient OPCs exhibited reduced calcium activity in response to stimulus in culture. Moreover, deletion of a TET1-5hmC target gene, Itpr2, an oligodendrocyte-enriched intracellular calcium-release channel, significantly impaired the onset of oligodendrocyte differentiation. Together, our results suggest that stage-specific TET1-mediated epigenetic programming and oligodendrocyte homeostasis is required for proper myelination and repair.

scholarly journals Transcriptome analysis identified long non-coding RNAs involved in the adaption of yak to high-altitude environments

2020 ◽  
Vol 7 (9) ◽  
pp. 200625
Author(s):  
Jin-Wei Xin ◽  
Zhi-Xin Chai ◽  
Cheng-Fu Zhang ◽  
Yu-Mei Yang ◽  
Qiang Zhang ◽  
...  
Keyword(s):  
Muscle Contraction ◽  
High Altitude ◽  
Target Genes ◽  
Calcium Release ◽  
Phosphoglycerate Mutase ◽  
Acid Oxidation ◽  
Transcriptional Level ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Kegg Pathways

The mechanisms underlying yak adaptation to high-altitude environments have been investigated using various methods, but no report has focused on long non-coding RNA (lncRNA). In the present study, lncRNAs were screened from the gluteus transcriptomes of yak and their transcriptional levels were compared with those in Sanjiang cattle, Holstein cattle and Tibetan cattle. The potential target genes of the differentially expressed lncRNAs between species/strains were predicted using cis and trans models. Based on cis -regulated target genes, no KEGG pathway was significantly enriched. Based on trans -regulated target genes, 11 KEGG pathways in relation to energy metabolism and three KEGG pathways associated with muscle contraction were significantly enriched. Compared with cattle strains, transcriptional levels of acyl-CoA dehydrogenase, acyl-CoA-binding protein, 3-hydroxyacyl-CoA dehydrogenase were relatively higher and those of glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate mutase 1, pyruvate kinase and lactate/malate dehydrogenase were relatively lower in yak, suggesting that yaks activated fatty acid oxidation but inhibited glucose oxidation and glycolysis. Besides, NADH dehydrogenase and ATP synthase showed lower transcriptional levels in yak than in cattle, which might protect muscle tissues from deterioration caused by reactive oxygen species (ROS). Compared with cattle strains, the higher transcriptional level of glyoxalase in yak might contribute to dicarbonyl stress resistance. Voltage-dependent calcium channel/calcium release channel showed a lower level in yak than in cattle strains, which could reduce the Ca 2+ influx and subsequently decrease the risk of hypertension. However, levels of EF-hand and myosin were higher in yak than in cattle strains, which might enhance the negative effects of reduced Ca 2+ on muscle contraction. Overall, the present study identified lncRNAs and proposed their potential regulatory functions in yak.

scholarly journals Ten-eleven translocation 1 mediated-DNA hydroxymethylation is required for myelination and remyelination in the mouse brain

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Zhang ◽  
Jian Wang ◽  
Kaixiang Zhang ◽  
Guozhen Lu ◽  
Yuming Liu ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Intracellular Signaling ◽  
System Development ◽  
Nervous System Development ◽  
Oligodendrocyte Progenitor Cells ◽  
Calcium Activity ◽  
Dna Hydroxymethylation ◽  
Tet Proteins ◽  
A Genome

AbstractTen-eleven translocation (TET) proteins, the dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role in myelination and remyelination after injury remains elusive. Here, we identify a genome-wide and locus-specific DNA hydroxymethylation landscape shift during differentiation of oligodendrocyte-progenitor cells (OPC). Ablation of Tet1 results in stage-dependent defects in oligodendrocyte (OL) development and myelination in the mouse brain. The mice lacking Tet1 in the oligodendrocyte lineage develop behavioral deficiency. We also show that TET1 is required for remyelination in adulthood. Transcriptomic, genomic occupancy, and 5-hydroxymethylcytosine (5hmC) profiling reveal a critical TET1-regulated epigenetic program for oligodendrocyte differentiation that includes genes associated with myelination, cell division, and calcium transport. Tet1-deficient OPCs exhibit reduced calcium activity, increasing calcium activity rescues the differentiation defects in vitro. Deletion of a TET1-5hmC target gene, Itpr2, impairs the onset of OPC differentiation. Together, our results suggest that stage-specific TET1-mediated epigenetic programming and intracellular signaling are important for proper myelination and remyelination in mice.

scholarly journals Immunoprecipitation and mass spectrometry define TET1 interactome during oligodendrocyte differentiation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ming Zhang ◽  
Kaixiang Zhang ◽  
Jian Wang ◽  
Yuming Liu ◽  
Guangxin Liu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
System Development ◽  
Protein Localization ◽  
Cellular Protein ◽  
Nervous System Development ◽  
Oligodendrocyte Differentiation ◽  
Dna Hydroxymethylation ◽  
Tet Proteins ◽  
Significant Enrichment ◽  
And Function

Abstract Ten-eleven translocation (TET) proteins, encoding dioxygenase for DNA hydroxymethylation, are important players in nervous system development and disease. In addition to their proverbial enzymatic role, TET proteins also possess non-enzymatic activity and function in multiple protein–protein interaction networks, which remains largely unknown during oligodendrocyte differentiation. To identify partners of TET1 in the myelinating cells, we performed proteome-wide analysis using co-immunoprecipitation coupled to mass spectrometry (IP-MS) in purified oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (mOLs), respectively. Following a stringent selection of MS data based on identification reliability and protein enrichment, we identified a core set of 1211 partners that specifically interact with TET1 within OPCs and OLs. Analysis of the biological process and pathways associated with TET1-interacting proteins indicates a significant enrichment of proteins involved in regulation of cellular protein localization, cofactor metabolic process and regulation of catabolic process, et al. We further validated TET1 interactions with selected partners. Overall, this comprehensive analysis of the endogenous TET1 interactome during oligodendrocyte differentiation suggest its novel mechanism in regulating oligodendrocyte homeostasis and provide comprehensive insight into the molecular pathways associated with TET1.

scholarly journals Immunoprecipitation and Mass Spectrometry Define TET1 Interactome During Oligodendrocyte Differentiation

2020 ◽  
Author(s):  
Ming Zhang ◽  
Kaixiang Zhang ◽  
Jian Wang ◽  
Yuming Liu ◽  
Guangxin Liu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
System Development ◽  
Protein Localization ◽  
Cellular Protein ◽  
Nervous System Development ◽  
Oligodendrocyte Differentiation ◽  
Dna Hydroxymethylation ◽  
Tet Proteins ◽  
Significant Enrichment ◽  
And Function

Abstract Ten-eleven translocation (TET) proteins, encoding dioxygenase for DNA hydroxymethylation, are important players in nervous system development and disease. In addition to their proverbial enzymatic role, TET proteins also possess non-enzymatic activity and function in multiple protein-protein interaction networks, which remains largely unknown during oligodendrocyte differentiation. To identify partners of TET1 in the myelinating cells, we performed proteome-wide analysis using co-immunoprecipitation coupled to mass spectrometry (IP-MS) in purified oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (mOLs), respectively. Following a stringent selection of MS data based on identification reliability and protein enrichment, we identified a core set of 1211 partners that specifically interact with TET1 within OPCs and OLs. Analysis of the biological process and pathways associated with TET1-interacting proteins indicates a significant enrichment of proteins involved in regulation of cellular protein localization, cofactor metabolic process and regulation of catabolic process, et al. We further validated TET1 interactions with selected partners. Overall, this comprehensive analysis of the endogenous TET1 interactome during oligodendrocyte differentiation suggest its novel mechanism in regulating oligodendrocyte homeostasis and provide comprehensive insight into the molecular pathways associated with TET1.

Association of Micro RNA and Postoperative Cognitive Dysfunction: A Review

2020 ◽  
Vol 20 (17) ◽  
pp. 1781-1790
Author(s):  
Noor Anisah Abu Yazit ◽  
Norsham Juliana ◽  
Srijit Das ◽  
Nur Islami Mohd Fahmi Teng ◽  
Nadia Mohd Fahmy ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Chromosomal Abnormalities ◽  
Current Knowledge ◽  
System Development ◽  
Genetic Disorder ◽  
Postoperative Cognitive Dysfunction ◽  
Clinical Importance ◽  
Nervous System Development ◽  
Micro Rna ◽  
A Genome

Postoperative Cognitive Dysfunction (POCD) refers to the condition of neurocognitive decline following surgery in a cognitive and sensory manner. There are several risk factors, which may be life-threatening for this condition. Neuropsychological assessment of this condition is very important. In the present review, we discuss the association of apolipoprotein epsilon 4 (APOE ε4) and few miRNAs with POCD, and highlight the clinical importance for prognosis, diagnosis and treatment of POCD. Microarray is a genome analysis that can be used to determine DNA abnormalities. This current technique is rapid, efficient and high-throughout. Microarray techniques are widely used to diagnose diseases, particularly in genetic disorder, chromosomal abnormalities, mutations, infectious diseases and disease-relevant biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are widely found distributed in eukaryotes. Few miRNAs influence the nervous system development, and nerve damage repair. Microarray approach can be utilized to understand the miRNAs involved and their pathways in POCD development, unleashing their potential to be considered as a diagnostic marker for POCD. This paper summarizes and identifies the studies that use microarray based approaches for POCD analysis. Since the application of microarray in POCD is expanding, there is a need to review the current knowledge of this approach.

scholarly journals Unravelling calcium-release channel gating: clues from a hot disease

2004 ◽  
Vol 380 (1) ◽  
pp. e1-e3 ◽  
Author(s):  
Tommie V. McCARTHY ◽  
John J. MACKRILL
Keyword(s):  
Calcium Release ◽  
Distinct Point ◽  
Ryanodine Receptors ◽  
Point Mutations ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Present Evidence ◽  
Gating Mechanism ◽  
Biochemical Journal ◽  
Interdomain Interactions

Ryanodine receptors (RyRs) are a family of intracellular channels that mediate Ca2+ release from the endoplasmic and sarcoplasmic reticulum. More than 50 distinct point mutations in one member of this family, RyR1, cause malignant hyperthermia, a potentially lethal pharmacogenetic disorder of skeletal muscle. These mutations are not randomly distributed throughout the primary structure of RyR1, but are grouped in three discrete clusters. In this issue of the Biochemical Journal, Kobayashi et al. present evidence that interdomain interactions between two of these mutation-enriched regions play a key role in the gating mechanism of RyR1.

scholarly journals Protein Kinase A Phosphorylation of the Cardiac Calcium Release Channel (Ryanodine Receptor) in Normal and Failing Hearts

2002 ◽  
Vol 278 (1) ◽  
pp. 444-453 ◽  
Author(s):  
Steven Reiken ◽  
Marta Gaburjakova ◽  
Silvia Guatimosim ◽  
Ana M. Gomez ◽  
Jeanine D'Armiento ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Ryanodine Receptor ◽  
Calcium Release ◽  
Calcium Release Channel ◽  
Release Channel ◽  
Kinase A
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