scholarly journals Polyadenylation of Histone H3.1 mRNA Promotes Cell Transformation by Displacing H3.3 from Gene Regulatory Elements

2019 ◽  
Author(s):  
Danqi Chen ◽  
Qiao Yi Chen ◽  
Zhenjia Wang ◽  
Yusha Zhu ◽  
Thomas Kluz ◽  
...  
Keyword(s):  
Cell Transformation ◽  
Regulatory Elements ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

scholarly journals Polyadenylation of Histone H3.1 mRNA Promotes Cell Transformation by Displacing H3.3 from Gene Regulatory Elements

2019 ◽  
Author(s):  
Danqi Chen ◽  
Qiao Yi Chen ◽  
Zhenjia Wang ◽  
Yusha Zhu ◽  
Thomas Kluz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Transformation ◽  
Regulatory Elements ◽  
Histone Variant ◽  
List Type ◽  
Cycle Arrest ◽  
Gene Regulatory Elements ◽  
Gene Regulatory ◽  
Canonical Histone

SummaryReplication-dependent canonical histone messenger RNAs (mRNAs) do not terminate with a poly(A) tail at the 3’ end. We previously demonstrated that exposure to arsenic, an environmental carcinogen, induces polyadenylation of canonical histone H3.1 mRNA. The addition of a poly(A) tail to the H3.1 mRNA caused transformation of human cells in vitro, but the underlying mechanisms are unknown. Here we report that polyadenylation of H3.1 mRNA increases H3.1 protein level, resulting in depletion of histone variant H3.3 at active promoters, enhancers, and insulator regions through its displacement. Cells underwent transcriptional deregulation, G2/M cell cycle arrest, chromosome aneuploidy and aberrations. Furthermore, knocking down the expression of H3.3 induced cell transformation, whereas ectopic expression of H3.3 attenuated arsenic-induced cell transformation, suggesting that H3.3 displacement might be central to tumorigenic effects of polyadenylated H3.1 mRNA. Our study provides novel insights into the importance of proper histone stoichiometry in maintaining genome integrity.HighlightsPolyadenylation of canonical histone H3.1 mRNA promotes tumor formation in nude miceHistone variant H3.3 is displaced from critical gene regulatory elements by overexpression of polyadenylated H3.1 mRNAIncreased polyadenylated H3.1 mRNA causes abnormal transcription, cell cycle arrest, and chromosomal instabilityArsenic induces polyadenylation of H3.1 mRNA in vivo

scholarly journals Polyadenylation of Histone H3.1 mRNA Promotes Cell Transformation by Displacing H3.3 from Gene Regulatory Elements

iScience ◽  
2020 ◽  
Vol 23 (9) ◽  
pp. 101518 ◽  
Author(s):  
Danqi Chen ◽  
Qiao Yi Chen ◽  
Zhenjia Wang ◽  
Yusha Zhu ◽  
Thomas Kluz ◽  
...  
Keyword(s):  
Cell Transformation ◽  
Regulatory Elements ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

Development of Integrative Map of MicroRNA Gene Regulatory Elements

MicroRNA ◽  
2016 ◽  
Vol 4 (3) ◽  
pp. 205-208 ◽  
Author(s):  
Minja Zorc ◽  
Tanja Kunej
Keyword(s):  
Regulatory Elements ◽  
Microrna Gene ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

scholarly journals Binding of an X-Specific Condensin Correlates with a Reduction in Active Histone Modifications at Gene Regulatory Elements

Genetics ◽  
2019 ◽  
Vol 212 (3) ◽  
pp. 729-742 ◽  
Author(s):  
Lena Annika Street ◽  
Ana Karina Morao ◽  
Lara Heermans Winterkorn ◽  
Chen-Yu Jiao ◽  
Sarah Elizabeth Albritton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Chromatin Immunoprecipitation ◽  
Protein Complexes ◽  
Regulatory Elements ◽  
Evolutionarily Conserved ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Gene Regulatory Elements ◽  
Gene Regulatory ◽  
Regulatory Sites

Condensins are evolutionarily conserved protein complexes that are required for chromosome segregation during cell division and genome organization during interphase. In Caenorhabditis elegans, a specialized condensin, which forms the core of the dosage compensation complex (DCC), binds to and represses X chromosome transcription. Here, we analyzed DCC localization and the effect of DCC depletion on histone modifications, transcription factor binding, and gene expression using chromatin immunoprecipitation sequencing and mRNA sequencing. Across the X, the DCC accumulates at accessible gene regulatory sites in active chromatin and not heterochromatin. The DCC is required for reducing the levels of activating histone modifications, including H3K4me3 and H3K27ac, but not repressive modification H3K9me3. In X-to-autosome fusion chromosomes, DCC spreading into the autosomal sequences locally reduces gene expression, thus establishing a direct link between DCC binding and repression. Together, our results indicate that DCC-mediated transcription repression is associated with a reduction in the activity of X chromosomal gene regulatory elements.

scholarly journals High-resolution mapping studies of chromatin and gene regulatory elements

Epigenomics ◽  
2009 ◽  
Vol 1 (2) ◽  
pp. 319-329 ◽  
Author(s):  
Alan P Boyle ◽  
Terrence S Furey
Keyword(s):  
High Resolution ◽  
Regulatory Elements ◽  
High Resolution Mapping ◽  
Gene Regulatory Elements ◽  
Resolution Mapping ◽  
Gene Regulatory

scholarly journals Identification and Computational Analysis of Gene Regulatory Elements

2015 ◽  
Vol 2015 (1) ◽  
pp. pdb.top083642 ◽  
Author(s):  
Leila Taher ◽  
Leelavati Narlikar ◽  
Ivan Ovcharenko
Keyword(s):  
Computational Analysis ◽  
Regulatory Elements ◽  
Gene Regulatory Elements ◽  
Gene Regulatory

Gene-regulatory elements may change the amount, timing, or location of gene expression, cis-Regulation therapy platforms might become a gene therapy to treat many genetic diseases

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Expression ◽  
Genetic Diseases ◽  
Regulatory Elements ◽  
Tissue Type ◽  
Gene Promoters ◽  
Expression Levels ◽  
Cis Regulation ◽  
Gene Regulatory Elements ◽  
Gene Regulatory ◽  
Gene Expression Levels

Changes in gene expression levels above or below a particular threshold may have a dramatic impact on phenotypes, leading to a wide spectrum of human illnesses. Gene-regulatory elements, also known as cis-regulatory elements (CREs), may change the amount, timing, or location (cell/tissue type) of gene expression, whereas mutations in a gene's coding sequence may result in lower or higher gene expression levels resulting in protein loss or gain. Loss-of-function mutations in both genes produce recessive human illness, while haploinsufficient mutations in 65 genes are also known to be deleterious due to function gain, according to the ClinVar1 and ClinGen3 databases. CREs are promoters living near to a gene's transcription start site and switching it on at predefined times, places, and levels. Other distal CREs, like enhancers and silencers, are temporal and tissue-specific control promoters. Enhancers activate promoters, commonly referred to as "promoters," whereas silencers turn them off. Insulators also restrict promiscuous interactions between enhancers and gene promoters. Systematic genomic approaches can help understand the cis-regulatory circuitry of gene expression by highly detecting and functionally defining these CREs. This includes the new use of CRISPR–CRISPR-associated protein 9 (CRISPR–Cas9) and other editing approaches to discover CREs. Cis-Regulation therapy (CRT) provides many promises to heal human ailments. CRT may be used to upregulate or downregulate disease-causing genes due to lower or higher levels of expression, and it may also be used to precisely adjust the expression of genes that assist in alleviating disease features. CRT may employ proteins that generate epigenetic modifications like methylation, histone modification, or gene expression regulation looping. Weighing CRT's advantages and downsides against alternative treatment methods is crucial. CRT platforms might become a practical technique to treat many genetic diseases that now lack treatment alternatives if academics, patient communities, clinicians, regulators and industry work together.

scholarly journals Discovery of gene regulatory elements through a new bioinformatics analysis of haploid genetic screens

PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0198463
Author(s):  
Bhaven B. Patel ◽  
Andres M. Lebensohn ◽  
Ganesh V. Pusapati ◽  
Jan E. Carette ◽  
Julia Salzman ◽  
...  
Keyword(s):  
Bioinformatics Analysis ◽  
Regulatory Elements ◽  
Genetic Screens ◽  
Gene Regulatory Elements ◽  
Gene Regulatory
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