scholarly journals Structural insights into the recognition of histone H3Q5 serotonylation by WDR5

2021 ◽  
Vol 7 (25) ◽  
pp. eabf4291
Author(s):  
Jie Zhao ◽  
Wanbiao Chen ◽  
Yi Pan ◽  
Yinfeng Zhang ◽  
Huiying Sun ◽  
...  
Keyword(s):  
Posttranslational Modification ◽  
Gene Activation ◽  
Histone H3 ◽  
Neuroblastoma Cells ◽  
Neuronal Cell ◽  
Promoter Regions ◽  
Unknown Mechanism ◽  
Neuronal Cell Differentiation ◽  
Induce Cell Proliferation ◽  
Structural Insights

Serotonylation of histone H3Q5 (H3Q5ser) is a recently identified posttranslational modification of histones that acts as a permissive marker for gene activation in synergy with H3K4me3 during neuronal cell differentiation. However, any proteins that specifically recognize H3Q5ser remain unknown. Here, we found that WDR5 interacts with the N-terminal tail of histone H3 and functions as a “reader” for H3Q5ser. Crystal structures of WDR5 in complex with H3Q5ser and H3K4me3Q5ser peptides revealed that the serotonyl group is accommodated in a shallow surface pocket of WDR5. Experiments in neuroblastoma cells demonstrate that H3K4me3 modification is hampered upon disruption of WDR5-H3Q5ser interaction. WDR5 colocalizes with H3Q5ser in the promoter regions of cancer-promoting genes in neuroblastoma cells, where it promotes gene transcription to induce cell proliferation. Thus, beyond revealing a previously unknown mechanism through which WDR5 reads H3Q5ser to activate transcription, our study suggests that this WDR5-H3Q5ser–mediated epigenetic regulation apparently promotes tumorigenesis.

scholarly journals Structural insights into the recognition of histone H3Q5 serotonylation by WDR5

2020 ◽  
Author(s):  
Jie Zhao ◽  
Wanbiao Chen ◽  
Yinfeng Zhang ◽  
Fan Yang ◽  
Nan Shen ◽  
...  
Keyword(s):  
Posttranslational Modification ◽  
Gene Activation ◽  
Histone H3 ◽  
Neuroblastoma Cells ◽  
Neuronal Cell ◽  
Promoter Regions ◽  
Unknown Mechanism ◽  
Neuronal Cell Differentiation ◽  
Induce Cell Proliferation ◽  
Structural Insights

AbstractSerotonylation of histone H3Q5 (H3Q5ser) is a recently identified posttranslational modification of histones that apparently acts as a permissive marker for gene activation in synergy with H3K4me3 during neuronal cell differentiation. However, any proteins which specifically recognize H3Q5ser remain unknown. Here, we discovered that WDR5 interacts with the N-terminal tail of histone H3 and functions as a ‘reader’ for H3Q5ser. Crystal structures of WDR5 in complex with H3Q5ser and H3K4me3Q5ser peptides revealed that the serotonyl group is accommodated in a shallow surface pocket of WDR5. Experiments in neuroblastoma cells demonstrate that WDR5 colocalizes with H3Q5ser in the promoter regions of cancer-promoting genes, where it promotes gene transcription to induce cell proliferation. Thus, beyond revealing a previously unknown mechanism through which WDR5 reads H3Q5ser to activate transcription, our study suggests that this WDR5-H3Q5ser mediated epigenetic regulation apparently promotes tumorigenesis.

scholarly journals 3D promoter architecture re-organization during iPSC-derived neuronal cell differentiation implicates target genes for neurodevelopmental disorders

2021 ◽  
pp. 102000
Author(s):  
Chun Su ◽  
Mariana Argenziano ◽  
Sumei Lu ◽  
James A. Pippin ◽  
Matthew C. Pahl ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Neurodevelopmental Disorders ◽  
Target Genes ◽  
Neuronal Cell ◽  
Promoter Architecture ◽  
Neuronal Cell Differentiation

scholarly journals Changes in the regulation of heat shock gene expression in neuronal cell differentiation

2008 ◽  
Vol 13 (1) ◽  
pp. 73-84 ◽  
Author(s):  
Jay Oza ◽  
Jingxian Yang ◽  
Kuang Yu Chen ◽  
Alice Y.-C. Liu
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
Heat Shock ◽  
Neuronal Cell ◽  
Heat Shock Gene ◽  
Neuronal Cell Differentiation ◽  
Shock Gene ◽  
Heat Shock Gene Expression

On the Application of Cultured Neuronal Cell Lines in Neurotoxicological Studies: Cytotoxicity of Acrylamide

1983 ◽  
Vol 11 (3) ◽  
pp. 135-145
Author(s):  
Erik Walum
Keyword(s):  
Cell Lines ◽  
Culture Medium ◽  
Neuroblastoma Cells ◽  
Neuronal Cell ◽  
Leucine Incorporation ◽  
Biochemical Process ◽  
Neurite Retraction ◽  
Mouse Neuroblastoma ◽  
Neuronal Cell Lines

Summary Acrylamide, a well known neurotoxic compound, was used in a first evaluation of cultured mouse neuroblastoma cells as an alternative to animal models for neurotoxicological studies. Hence, the effects of acrylamide on the growth, size, morphology and leucine incorporation of three neuroblastoma (41A3, N18 and N1E115), one neuroblastoma x glioma hybrid (NG108CC15), two glioma (138MG and C6) and two fibroblast (RLF and RMC) cell lines were studied. It was found that the concentration of acrylamide needed to inhibit the growth by 50% in 24 hr was similar in all cell lines, i.e. around 2 x 10-4g/ml culture medium. In the two cell lines, N1E115 and NG108CC15, acrylamide at this concentration caused neurite retraction and at higher concentrations (5 x 10-4g/ml) a decrease in cell viability. In a concentration range of 5 x 10-5 - 5 x 10-4g/ml acrylamide did not affect cell size, or at 2 x 10-4g/ml incorporation of leucine into trichloroacetic acid precipitable material. It is suggested that acrylamide interferes with a biochemical process common to all the tested cells, but of greater importance in differentiated nerve cells than in others. Whether this process is consistent with the in vivo target for the neurotoxic action of acrylamide remains to be unravelled.

scholarly journals Structural Insights into Histone H3 Lysine 56 Acetylation by Rtt109

Structure ◽  
2008 ◽  
Vol 16 (10) ◽  
pp. 1503-1510 ◽  
Author(s):  
Chengqi Lin ◽  
Y. Adam Yuan
Keyword(s):  
Histone H3 ◽  
Structural Insights

scholarly journals Neuronal cell differentiation of mesenchymal stem cells originating from canine amniotic fluid

Human Cell ◽  
2013 ◽  
Vol 27 (2) ◽  
pp. 51-58 ◽  
Author(s):  
Eun Young Kim ◽  
Kyung-Bon Lee ◽  
Jung Yu ◽  
Ji Hye Lee ◽  
Keun Jung Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Differentiation ◽  
Amniotic Fluid ◽  
Neuronal Cell ◽  
Neuronal Cell Differentiation

Effect of Channa argus Extracts From Different Extraction Processes on Neuronal Cell Differentiation and Oxidative Stress

2021 ◽  
Vol 25 (3) ◽  
pp. 178-187
Author(s):  
Kyoung Hwan Cho ◽  
Young-Sool Hah ◽  
Eun-Ji Kim ◽  
Seung-Jun Lee ◽  
Ho Jin Choo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Differentiation ◽  
Neuronal Cell ◽  
Neuronal Cell Differentiation ◽  
Channa Argus ◽  
Extraction Processes ◽  
And Oxidative Stress

scholarly journals LIN28B regulates transcription and potentiates MYCN-induced neuroblastoma through binding to ZNF143 at target gene promotors

2020 ◽  
Vol 117 (28) ◽  
pp. 16516-16526 ◽  
Author(s):  
Ting Tao ◽  
Hui Shi ◽  
Luca Mariani ◽  
Brian J. Abraham ◽  
Adam D. Durbin ◽  
...  
Keyword(s):  
Neuroblastoma Cells ◽  
Neuronal Cell ◽  
Distant Metastases ◽  
Malignant Cell ◽  
Gene Promoters ◽  
Invasion And Migration ◽  
Protein Protein Interaction ◽  
Cell Adhesion And Migration ◽  
And Migration

LIN28B is highly expressed in neuroblastoma and promotes tumorigenesis, at least, in part, through inhibition oflet-7microRNA biogenesis. Here, we report that overexpression of either wild-type (WT) LIN28B or a LIN28B mutant that is unable to inhibitlet-7processing increases the penetrance of MYCN-induced neuroblastoma, potentiates the invasion and migration of transformed sympathetic neuroblasts, and drives distant metastases in vivo. Genome-wide chromatin immunoprecipitation coupled with massively parallel DNA sequencing (ChIP-seq) and coimmunoprecipitation experiments show that LIN28B binds active gene promoters in neuroblastoma cells through protein–protein interaction with the sequence-specific zinc-finger transcription factor ZNF143 and activates the expression of downstream targets, including transcription factors forming the adrenergic core regulatory circuitry that controls the malignant cell state in neuroblastoma as well asGSK3BandL1CAMthat are involved in neuronal cell adhesion and migration. These findings reveal an unexpectedlet-7–independent function of LIN28B in transcriptional regulation during neuroblastoma pathogenesis.

scholarly journals The Roles of the Histone Protein Modifier EZH2 in the Uterus and Placenta

Epigenomes ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 20
Author(s):  
Ana M. Mesa ◽  
Cheryl S. Rosenfeld ◽  
Geetu Tuteja ◽  
Theresa I. Medrano ◽  
Paul S. Cooke
Keyword(s):  
Critical Role ◽  
Histone H3 ◽  
Gene Promoter ◽  
Epigenetic Changes ◽  
Promoter Regions ◽  
Polycomb Repressive Complex 2 ◽  
Gene Sets ◽  
Ezh2 Expression ◽  
And Function ◽  
Transcription Enhancer

Epigenetic modifications regulate normal physiological, as well as pathological processes in various organs, including the uterus and placenta. Both organs undergo dramatic and rapid restructuring that depends upon precise orchestration of events. Epigenetic changes that alter transcription and translation of gene-sets regulate such responses. Histone modifications alter the chromatin structure, thereby affecting transcription factor access to gene promoter regions. Binding of histones to DNA is regulated by addition or removal of subunit methyl and other groups, which can inhibit or stimulate transcription. Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2) that catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) and subsequently suppresses transcription of genes bound by such histones. Uterine EZH2 expression exerts a critical role in development and function of this organ with deletion of this gene resulting in uterine hyperplasia and expression of cancer-associated transcripts. Elucidating the roles of EZH2 in uterus and placenta is essential as EZH2 dysregulation is associated with several uterine and placental pathologies. Herein, we discuss EZH2 functions in uterus and placenta, emphasizing its physiological and pathological importance.

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