scholarly journals DNA Hydroxymethylation in the Regulation of Gene Expression in Human Solid Cancer

Author(s):  
Sofia L. Alcaraz-Estrada ◽  
Gabriela Leija-Montoya ◽  
Nicolás Serafín-Higuera ◽  
Silvia García ◽  
Claudia E. Millán-Testa ◽  
...  
2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Christopher G. Chapman ◽  
Christopher J. Mariani ◽  
Feng Wu ◽  
Katherine Meckel ◽  
Fatma Butun ◽  
...  

Abstract The formation of differentiated cell types from pluripotent progenitors involves epigenetic regulation of gene expression. DNA hydroxymethylation results from the enzymatic oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) 5-mC dioxygenase enzymes. Previous work has mapped changes in 5-mC during differentiation of intestinal stem cells. However, whether or not 5-hmC regulates colonocyte differentiation is unknown. Here we show that 5-hmC regulates gene expression during colonocyte differentiation and controls gene expression in human colon cancers. Genome-wide profiling of 5-hmC during in vitro colonic differentiation demonstrated that 5-hmC is gained at highly expressed and induced genes and is associated with intestinal transcription factor binding sites, including those for HNF4A and CDX2. TET1 induction occurred during differentiation and TET1 knockdown altered gene expression and inhibited barrier formation of colonocytes. We find that the 5-hmC distribution in primary human colonocytes parallels the distribution found in differentiated cells in vitro and that gene-specific 5-hmC changes in human colon cancers are directly correlated with changes in gene expression. Our results support a model in which 5-hmC regulates differentiation of adult human intestine and 5-hmC alterations contribute to the disrupted gene expression in colon cancer.


2020 ◽  
Vol 477 (16) ◽  
pp. 3091-3104 ◽  
Author(s):  
Luciana E. Giono ◽  
Alberto R. Kornblihtt

Gene expression is an intricately regulated process that is at the basis of cell differentiation, the maintenance of cell identity and the cellular responses to environmental changes. Alternative splicing, the process by which multiple functionally distinct transcripts are generated from a single gene, is one of the main mechanisms that contribute to expand the coding capacity of genomes and help explain the level of complexity achieved by higher organisms. Eukaryotic transcription is subject to multiple layers of regulation both intrinsic — such as promoter structure — and dynamic, allowing the cell to respond to internal and external signals. Similarly, alternative splicing choices are affected by all of these aspects, mainly through the regulation of transcription elongation, making it a regulatory knob on a par with the regulation of gene expression levels. This review aims to recapitulate some of the history and stepping-stones that led to the paradigms held today about transcription and splicing regulation, with major focus on transcription elongation and its effect on alternative splicing.


2011 ◽  
Vol 33 (12) ◽  
pp. 1300-1307
Author(s):  
Xiu-Jun ZHANG ◽  
Mei-Ling LIU ◽  
Meng-Chun JIA

2017 ◽  
Vol 63 (5) ◽  
pp. 695-702
Author(s):  
Oleg Kit ◽  
Dmitriy Vodolazhskiy ◽  
Yelena Frantsiyants ◽  
Svetlana Panina ◽  
E. Rastorguev ◽  
...  

Glioblastoma multiforme (GBM) is the most common and invasive poorly differentiated brain tumor with nearly 100 % rate of recurrence and unfavorable prognosis. The aim of the present review is to analyze recent studies and experimental results (Scopus, Web of Science, PubMed) concerning somatic mutations in glioblastoma, aberrant regulation of gene expression of signal pathways including EGFR, TGFß, etc. and markers for GBM progression. Particularly the molecular subtypes of glioblastoma and NGS results are considered in this review.


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