DNA Mismatch Binding and Incision at Modified Guanine Bases by Extracts of Mammalian Cells: Implications for Tolerance to DNA Methylation Damage

Biochemistry ◽  
1994 ◽  
Vol 33 (16) ◽  
pp. 4787-4793 ◽  
Author(s):  
Shaun Griffin ◽  
Pauline Branch ◽  
Yao-Zhong Xu ◽  
Peter Karran
Keyword(s):  
Dna Methylation ◽  
Mammalian Cells ◽  
Dna Mismatch

scholarly journals Control of the DNA Methylation System Component MBD2 by Protein Arginine Methylation

2006 ◽  
Vol 26 (19) ◽  
pp. 7224-7235 ◽  
Author(s):  
Choon Ping Tan ◽  
Sara Nakielny
Keyword(s):  
Dna Methylation ◽  
Complex Formation ◽  
Histone Deacetylases ◽  
Mammalian Cells ◽  
Genome Stability ◽  
Epigenetic Modification ◽  
Arginine Methylation ◽  
System Component ◽  
Transcription Repression ◽  
Mbd Proteins

ABSTRACT DNA methylation is vital for proper chromatin structure and function in mammalian cells. Genetic removal of the enzymes that catalyze DNA methylation results in defective imprinting, transposon silencing, X chromosome dosage compensation, and genome stability. This epigenetic modification is interpreted by methyl-DNA binding domain (MBD) proteins. MBD proteins respond to methylated DNA by recruiting histone deacetylases (HDAC) and other transcription repression factors to the chromatin. The MBD2 protein is dispensable for animal viability, but it is implicated in the genesis of colon tumors. Here we report that the MBD2 protein is controlled by arginine methylation. We identify the protein arginine methyltransferase enzymes that catalyze this modification and show that arginine methylation inhibits the function of MBD2. Arginine methylation of MBD2 reduces MBD2-methyl-DNA complex formation, reduces MBD2-HDAC repression complex formation, and impairs the transcription repression function of MBD2 in cells. Our report provides a molecular description of a potential regulatory mechanism for an MBD protein family member. It is the first to demonstrate that protein arginine methyltransferases participate in the DNA methylation system of chromatin control.

Escherichia coli and colorectal cancer: Unfolding the enigmatic relationship

2021 ◽  
Vol 22 ◽  
Author(s):  
Rogayeh Nouri ◽  
Alka Hasani ◽  
Kourosh Masnadi Shirazi ◽  
Mohammad Reza Aliand ◽  
Bita Sepehri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Escherichia Coli ◽  
Mammalian Cells ◽  
Chromosomal Rearrangements ◽  
Current Evidence ◽  
Dna Breaks ◽  
Colon Cells ◽  
E Coli ◽  
Dna Mismatch ◽  
Double Strand Dna Breaks

: Colorectal cancer (CRC) is one of the deadliest cancers in the world. Specific strains of intestinal Escherichia coli (E. coli) may influence the initiation and development of CRC by exploiting virulence factors and inflammatory pathways. Mucosa-associated E. coli strains are more prevalent in CRC biopsies in comparison to healthy controls. Moreover, these strains can survive and replicate within macrophages and induce a pro-inflammatory response. Chronic exposure to inflammatory mediators can lead to increased cell proliferation and cancer. Production of colobactin toxin by the majority of mucosa-associated E. coli isolated from CRC patients is another notable finding. Colibactin-producing E. coli strains, in particular, induce double-strand DNA breaks, stop the cell cycle, involve in chromosomal rearrangements of mammalian cells and are implicated in carcinogenic effects in animal models. Moreover, some enteropathogenic E. coli (EPEC) strains are able to survive and replicate in colon cells as chronic intracellular pathogens and may promote susceptibility to CRC by downregulation of DNA Mismatch Repair (MMR) proteins. In this review, we discuss current evidence and focus on the mechanisms by which E. coli can influence the development of CRC.

scholarly journals DNA methylation directs microRNA biogenesis in mammalian cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ohad Glaich ◽  
Shivang Parikh ◽  
Rachel E. Bell ◽  
Keren Mekahel ◽  
Maya Donyo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Mammalian Cells ◽  
Sequence Conservation ◽  
Mirna Biogenesis ◽  
Coding Sequence ◽  
Microrna Biogenesis ◽  
Flanking Regions

AbstractMicroRNA (miRNA) biogenesis initiates co-transcriptionally, but how the Microprocessor machinery pinpoints the locations of short precursor miRNA sequences within long flanking regions of the transcript is not known. Here we show that miRNA biogenesis depends on DNA methylation. When the regions flanking the miRNA coding sequence are highly methylated, the miRNAs are more highly expressed, have greater sequence conservation, and are more likely to drive cancer-related phenotypes than miRNAs encoded by unmethylated loci. We show that the removal of DNA methylation from miRNA loci leads to their downregulation. Further, we found that MeCP2 binding to methylated miRNA loci halts RNA polymerase II elongation, leading to enhanced processing of the primary miRNA by Drosha. Taken together, our data reveal that DNA methylation directly affects miRNA biogenesis.

Methylation Profile of B-Chronic Lymphocytic Leukemia Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2951-2951
Author(s):  
Jun Fan ◽  
Asou Norio ◽  
Masao Matsuoka
Keyword(s):  
Dna Methylation ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Lines ◽  
Mammalian Cells ◽  
Mononuclear Cells ◽  
Cpg Island ◽  
Methylation Status ◽  
Lymphocytic Leukemia ◽  
Dna Hypomethylation ◽  
Peripheral Blood Mononuclear

Abstract DNA methylation plays an important role in the development and aging of mammalian cells, and its dysregulation has been frequently observed in cancer cells. The purpose of this study is to investigate the involvement of aberrant DNA methylation in B chronic lymphocytic leukemia (B-CLL) cells. We compared methylation status of B-CLL cells isolated from patients with that of normal CD19+ cells isolated from health donors by methylated CpG island amplification/representative difference analysis method. 5 hypermethylated and 27 hypomethylated DNA regions were identified in B-CLL sample. Among the 27 hypomethylated regions, 5 located on chromosome 9q34, 3 on 10q25-26 and 4 on 19q13. Methylation status was confirmed by sequencing using sodium bisulfite-treated DNA samples. By comparing DNA samples from same patients at different clinical stages, we found that lower methylation density in these regions is linked with disease progression. Expression of 15 genes surrounding hypomethylated regions was studied by RT-PCR. Expression of laminin beta3 gene and melanotransferrin gene was found to be upregulated in all B-CLL cell lines as well as lymphoma cell lines comparing with normal CD19+ peripheral blood mononuclear cells. B-cell CLL/lymphoma 11b gene showed increased expression in only 2 B-CLL cell lines. For other genes, no transcriptional change was found regardless of changed DNA methylation. This study showed the predominance of DNA hypomethylation in B-CLL cells compared with hypermethylation. Hypomethylated regions clustered in a limited number of chromosomes and methylation density appeared to be inversely correlated with disease progress. Figure Figure

scholarly journals HMPL: A Pipeline for Identifying Hemimethylation Patterns by Comparing Two Samples

2015 ◽  
Vol 14s2 ◽  
pp. CIN.S17286 ◽  
Author(s):  
Shuying Sun ◽  
Peng Li
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mammalian Cells ◽  
Single Sample ◽  
Methyl Group ◽  
Genome Wide ◽  
Two Samples ◽  
Clustering Patterns

DNA methylation (the addition of a methyl group to a cytosine) is an important epigenetic event in mammalian cells because it plays a key role in regulating gene expression. Most previous methylation studies assume that DNA methylation occurs on both positive and negative strands. However, a few studies have reported that in some genes, methylation occurs only on one strand (ie, hemimethylation) and has clustering patterns. These studies report that hemimethylation occurs on individual genes. It is unclear whether hemimethylation occurs genome-wide and whether there are hemimethylation differences between cancerous and noncancerous cells. To address these questions, we have developed the first-ever pipeline, named hemimethylation pipeline (HMPL), to identify hemimethylation patterns. Utilizing the available software and the newly developed Perl and R scripts, HMPL can identify hemimethylation patterns for a single sample and can also compare two different samples.

Delayed DNA methylation is an integral feature of DNA replication in mammalian cells

1986 ◽  
Vol 166 (1) ◽  
pp. 103-112 ◽  
Author(s):  
D.M. Woodcock ◽  
D.L. Simmons ◽  
P.J. Crowther ◽  
I.A. Cooper ◽  
K.J. Trainor ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Replication ◽  
Mammalian Cells ◽  
Integral Feature

scholarly journals Methylation-Mediated Transcriptional Silencing in Euchromatin by Methyl-CpG Binding Protein MBD1 Isoforms

1999 ◽  
Vol 19 (9) ◽  
pp. 6415-6426 ◽  
Author(s):  
Naoyuki Fujita ◽  
Shin-ichiro Takebayashi ◽  
Katsuzumi Okumura ◽  
Shinichi Kudo ◽  
Tsutomu Chiba ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transcriptional Repression ◽  
Mammalian Cells ◽  
Fluorescent Protein ◽  
Cpg Islands ◽  
Transcriptional Silencing ◽  
Pericentromeric Region ◽  
Chromosome 1 ◽  
Reverse Transcription Pcr ◽  
Genome Methylation

ABSTRACT DNA methylation of promoter-associated CpG islands is involved in the transcriptional repression of vertebrate genes. To investigate the mechanisms underlying gene inactivation by DNA methylation, we characterized a human MBD1 protein, one of the components of MeCP1, which possesses a methyl-CpG binding domain (MBD) and cysteine-rich (CXXC) domains. Four novel MBD1 isoforms (MBD1v1, MBD1v2, MBD1v3, and MBD1v4) were identified by the reverse transcription-PCR method. We found that these transcripts were alternatively spliced in the region of CXXC domains and the C terminus. Green fluorescent protein-fused MBD1 was localized to multiple foci on the human genome, mostly in the euchromatin regions, and particularly concentrated in the pericentromeric region of chromosome 1. Both the MBD sequence and genome methylation were required for proper localization of the MBD1 protein. We further investigated whether MBD1 isoforms are responsible for transcriptional repression of human genes. A bacterially expressed MBD1 protein bound preferentially to methylated DNA fragments containing CpG islands from the tumor suppressor genes p16,VHL, and E-cadherin and from an imprintedSNRPN gene. All MBD1 isoforms inhibited promoter activities of these genes via methylation. Interestingly, MBD1 isoforms v1 and v2 containing three CXXC domains also suppressed unmethylated promoter activities in mammalian cells. These effects were further manifested inDrosophila melanogaster cells, which lack genome methylation. Sp1-activated transcription of methylated p16and SNRPN promoters was inhibited by all of the MBD1 isoforms, whereas the isoforms v1 and v2 reduced Sp1-activated transcription from unmethylated promoters as well. These findings suggested that the MBD1 isoforms have different roles in methylation-mediated transcriptional silencing in euchromatin.

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