scholarly journals CIC is a Critical Regulator of Neuronal Differentiation

2019 ◽  
Author(s):  
Inah Hwang ◽  
Heng Pan ◽  
Jun Yao ◽  
Olivier Elemento ◽  
Hongwu Zheng ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Transcriptional Repression ◽  
High Mobility ◽  
Neural Progenitor Cell ◽  
Mass Spectrometry Analysis ◽  
Transcriptional Repressors ◽  
Spectrometry Analysis ◽  
Corepressor Complex ◽  
Progenitor Cell Proliferation ◽  
Neuronal Lineage

ABSTRACTCapicua (CIC), a member of the high mobility group (HMG)-box superfamily of transcriptional repressors, is frequently mutated in human oligodendrogliomas. But its function in brain development and tumorigenesis remains poorly understood. Here, we report that brain-specific deletion of Cic compromises developmental transition of neuroblast to immature neurons in mouse hippocampus and compromises normal neuronal differentiation. Combined gene expression and ChIP-seq analyses identified VGF as an important CIC-repressed transcriptional surrogates involved in neuronal lineage regulation. Aberrant VGF expression promotes neural progenitor cell proliferation by suppressing their differentiation. Mechanistically, we demonstrated that CIC represses VGF expression by tethering SIN3-HDAC to form a transcriptional corepressor complex. Mass spectrometry analysis of CIC-interacting proteins further identified BRG1 containing mSWI/SNF complex of which function is necessary for transcriptional repression by CIC. Together, this study uncovers a novel regulatory pathway of CIC-dependent neuronal differentiation and provides molecular insights into the etiology of CIC-dependent brain tumors.

scholarly journals TAZ Represses the Neuronal Commitment of Neural Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2230
Author(s):  
Natalia Robledinos-Antón ◽  
Maribel Escoll ◽  
Kun-Liang Guan ◽  
Antonio Cuadrado
Keyword(s):  
Neuronal Differentiation ◽  
Subventricular Zone ◽  
Transcriptional Repression ◽  
Genetic Manipulation ◽  
Mammalian Brain ◽  
Additional Function ◽  
Neural Stem Progenitor Cells ◽  
Neuronal Lineage ◽  
Neuronal Commitment

The mechanisms involved in regulation of quiescence, proliferation, and reprogramming of Neural Stem Progenitor Cells (NSPCs) of the mammalian brain are still poorly defined. Here, we studied the role of the transcriptional co-factor TAZ, regulated by the WNT and Hippo pathways, in the homeostasis of NSPCs. We found that, in the murine neurogenic niches of the striatal subventricular zone and the dentate gyrus granular zone, TAZ is highly expressed in NSPCs and declines with ageing. Moreover, TAZ expression is lost in immature neurons of both neurogenic regions. To characterize mechanistically the role of TAZ in neuronal differentiation, we used the midbrain-derived NSPC line ReNcell VM to replicate in a non-animal model the factors influencing NSPC differentiation to the neuronal lineage. TAZ knock-down and forced expression in NSPCs led to increased and reduced neuronal differentiation, respectively. TEADs-knockdown indicated that these TAZ co-partners are required for the suppression of NSPCs commitment to neuronal differentiation. Genetic manipulation of the TAZ/TEAD system showed its participation in transcriptional repression of SOX2 and the proneuronal genes ASCL1, NEUROG2, and NEUROD1, leading to impediment of neurogenesis. TAZ is usually considered a transcriptional co-activator promoting stem cell proliferation, but our study indicates an additional function as a repressor of neuronal differentiation.

Mass spectrometry analysis of redox forms of High-Mobility Group Box-1 Protein in cerebrospinal fluid: initial experience.

2019 ◽  
Vol 88 (3) ◽  
pp. 171-176
Author(s):  
Agata Światły ◽  
Norbert Wąsik ◽  
Joanna Hajduk ◽  
Eliza Matuszewska ◽  
Paweł Dereziński ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
High Mobility ◽  
High Mobility Group ◽  
Mass Spectrometry Analysis ◽  
Aneurysmal Subarachnoid Haemorrhage ◽  
Top Down ◽  
Spectrometry Analysis ◽  
Redox Forms

Introduction. High-mobility group box 1 (HMGB1) is an alarmin with proinflammatory potential determined by redox status of the cysteines at position 23 and 45. It may also play a role as a biomarker in biological fluids. The aim of this study was the identification of different HMGB1 redox forms in cerebrospinal fluid (CSF) obtained from subarachnoid hemorrhage patients. Material and Methods. 6 CSF samples were collected from aneurysmal subarachnoid haemorrhage patients. Commercially available HMGB1 isoforms served as a positive control. Immunoprecipitation and electrophoretic isolation of HMGB1 protein were performed, then both CSF and control were analyzed using mass spectrometry technique. To distinguish between fully reduced (thiol group at C23 and C45) and disulfide (disulfide bond connecting C23 and C45) HMGB1 forms, top-down sequencing of the spectra was performed. Results. Top-down sequencing analysis allowed to distinguish between HMGB1 isoforms only in commercially available standard without preceding immunoprecipitation and electrophoresis. MALDI spectra differ i.e. on the fully reduced HMGB1 spectrum fragmentation occurs before and beyond C22, which is not present on the disulfide HMGB1 spectrum. Analysis of HMGB1 isolated from CSF obtained from subarachnoid hemorrhage patients gave no results. Conclusions. Top-down sequencing enables to distinguish between redox forms of HMGB1. Electrophoresis and tryptic digestion cannot precede mass spectrometry analysis of redox forms of HMGB1 due to the reduction of disulfide bonds during these processes. Preferred method of isolation of HMGB1 for direct analysis using top-down sequencing mustn’t include protein digestion or degradation.

FGF‐4 regulates neural progenitor cell proliferation and neuronal differentiation

2006 ◽  
Vol 20 (9) ◽  
pp. 1484-1485 ◽  
Author(s):  
Nobuyoshi Kosaka ◽  
Maho Kodama ◽  
Hideo Sasaki ◽  
Yusuke Yamamoto ◽  
Fumitaka Takeshita ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Neuronal Differentiation ◽  
Progenitor Cell ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Progenitor Cell Proliferation

Arginine Methylation of Runx1 Regulates Its Biological and Transcriptional Activities.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2041-2041
Author(s):  
Xinyang Zhao ◽  
Animesh Parkanani ◽  
Jin Zhang ◽  
Richard Dunne ◽  
Andrew Xiao ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Arginine Methylation ◽  
Serine Phosphorylation ◽  
Context Dependency ◽  
Mass Spectrometry Analysis ◽  
Runt Domain ◽  
Spectrometry Analysis ◽  
Gene Reporter Assay ◽  
Arginine Residues

Abstract The AML1/Runx1 protein is required for definitive hematopoiesis and for the maturation of adult megakaryocytic cells. Alterations of the Runx1 gene by mutations, deletions and chromosome translocations are associated with several types of acute leukemia. Runx1 functions as both an activator and repressor of gene transcription with promoter and cell type context dependency. Likely, this relates to the ability of Runx1 to interact with a variety of transcription factors such as MEF, C/EBPa, Ets-1 and GATA-1 and also with repressor proteins such as Groucho, mSin3 and HDACs. Runx1 is post-translationally modified through acetylation and phosphorylation, and the acetylable and phosphorylable forms of Runx1 can activate transcription to higher level in Runx1 dependent reporter assays when HATs or Erk2 are coexpressed. Runx1 has also been shown to be methylated on lysine residues by SUV39H1 methyltransferase in fibroblasts. Based on the presence of a SGRGK motif in the runt domain of Runx1, we have been examining whether Runx1 is methylated on arginine residues by the protein arginine methyltransferases (PRMT). We have found that PRMT1 and PRMT5 are associated with Runx1 in AML cells by co-immunoprecipitation assays and using in vitro by GST-pulldown assays with in vitro translated PRMT(s) have shown that the interactions are direct. Using a luciferase gene reporter assay, we show that PRMT1 acts synergistically with p300 to activate Runx1 mediated transcription in response to cell proliferation signals. We have mapped the arginine methylation sites in Runx1 using GST-Runx1 fusion proteins, site-specific mutagenesis and mass spectrometry analysis. We have found three potential arginine methylation sites, one in the Runt domain, and two in the Runx1 carboxy-terminal region. Interestingly, one of these sites is in the region shown to interact with both the mSIN3A transcriptional repression complex and with p300. This suggests that arginine methylation of Runx1 may affects its transcriptional activating and repressing functions. Chromatin immunoprecipitation assays are underway to show how arginine methylation of Runx1 affects its activities in hematopoietic cells. Additional studies examining the effects of cross-talk between arginine methylation, lysine acetylation and serine phosphorylation has on Runx1 functions (biological and biochemical) will be presented.

scholarly journals Neurogenin 1 Mediates Erythropoietin Enhanced Differentiation of Adult Neural Progenitor Cells

2005 ◽  
Vol 26 (4) ◽  
pp. 556-564 ◽  
Author(s):  
Lei Wang ◽  
Zheng G Zhang ◽  
Rui L Zhang ◽  
Zhong X Jiao ◽  
Ying Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Neurite Outgrowth ◽  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Progenitor Cell ◽  
Neural Progenitor Cells ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Mrna Levels ◽  
Progenitor Cell Proliferation

Proneuronal basic helix–loop–helix (bHLH) transcription factor, neurogenin 1 (Ngn1), regulates neuronal differentiation during development of the cerebral cortex. Akt mediates proneuronal bHLH protein function to promote neuronal differentiation. Here, we show that recombinant human erythropoietin (rhEPO) significantly increased Akt activity and Ngn1 mRNA levels in neural progenitor cells derived from the subventricular zone (SVZ) of adult rat, which was coincident with increases of neural progenitor cell proliferation, differentiation, and neurite outgrowth. Inhibition of Akt activity by the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) inhibitor, LY294002, abolished rhEPO-increased Ngn1 mRNA levels and the effects of rhEPO on neural progenitor cells. In addition, reducing expression of endogenous Ngn1 by means of short-interfering RNA (siRNA) blocked rhEPO-enhanced neuronal differentiation and neurite outgrowth but not rhEPO-increased proliferation. Furthermore, treatment of stroke rat with rhEPO significantly increased Ngn1 mRNA levels in SVZ cells. These data suggest that rhEPO acts as an extracellular molecule that activates the PI3K/Akt pathway, which enhances adult neural progenitor cell proliferation, differentiation, and neurite outgrowth, and Ngn1 is required for Akt-mediated neuronal differentiation and neurite outgrowth.

Spectrophotometry Measurement of Polynuclear Aromatic Hydrocarbons in Hamilton Harbour Sediments

1991 ◽  
Vol 26 (1) ◽  
pp. 1-16 ◽  
Author(s):  
T.P. Murphy ◽  
H. Brouwer ◽  
M.E. Fox ◽  
E. Nagy
Keyword(s):  
Aromatic Hydrocarbons ◽  
Total Concentration ◽  
Coal Tar ◽  
Sediment Cores ◽  
Polynuclear Aromatic Hydrocarbons ◽  
Mass Spectrometry Analysis ◽  
Gas Chromatography Mass Spectrometry ◽  
Near Surface ◽  
Spectrometry Analysis ◽  
Hamilton Harbour

Abstract Eighty-one sediment cores were collected to determine the extent of coal tar contamination in a toxic area of Hamilton Harbour. Over 800 samples were analyzed by a UV spectrophotometric technique that was standardized with gas chromatography/mass spectrometry analysis. The coal tar distribution was variable. The highest concentrations were near the Stelco outfalls and the Hamilton-Wentworth combined sewer outfalls. The total concentration of the 16 polynuclear aromatic hydrocarbons (PAHs) in 48,300 m3 of near-surface sediments exceeded 200 µg/g.

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