Saturation Screening of the Druggable Mammalian Genome

2005 ◽  
pp. 251-278
Author(s):  
Hector Beltrandelrio ◽  
Francis Kern ◽  
Thomas Lanthorn ◽  
Tamas Oravecz ◽  
James Piggott ◽  
...  
Keyword(s):  
Mammalian Genome

scholarly journals DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wendan Ren ◽  
Huitao Fan ◽  
Sara A. Grimm ◽  
Jae Jin Kim ◽  
Linhui Li ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Histone H3 ◽  
Genomic Stability ◽  
Mammalian Genome ◽  
Dna Methyltransferase 1 ◽  
Chromatin Modifications ◽  
Direct Link ◽  
Histone H4 ◽  
Radiation Induced

AbstractDNA methylation and trimethylated histone H4 Lysine 20 (H4K20me3) constitute two important heterochromatin-enriched marks that frequently cooperate in silencing repetitive elements of the mammalian genome. However, it remains elusive how these two chromatin modifications crosstalk. Here, we report that DNA methyltransferase 1 (DNMT1) specifically ‘recognizes’ H4K20me3 via its first bromo-adjacent-homology domain (DNMT1BAH1). Engagement of DNMT1BAH1-H4K20me3 ensures heterochromatin targeting of DNMT1 and DNA methylation at LINE-1 retrotransposons, and cooperates with the previously reported readout of histone H3 tail modifications (i.e., H3K9me3 and H3 ubiquitylation) by the RFTS domain to allosterically regulate DNMT1’s activity. Interplay between RFTS and BAH1 domains of DNMT1 profoundly impacts DNA methylation at both global and focal levels and genomic resistance to radiation-induced damage. Together, our study establishes a direct link between H4K20me3 and DNA methylation, providing a mechanism in which multivalent recognition of repressive histone modifications by DNMT1 ensures appropriate DNA methylation patterning and genomic stability.

scholarly journals Introduction to Mammalian Genome special issue: inflammation and immunity in cancer

2018 ◽  
Vol 29 (11-12) ◽  
pp. 691-693
Author(s):  
Andreas Behren ◽  
Daniel Speidel ◽  
George Kollias ◽  
Viive M. Howell
Keyword(s):  
Mammalian Genome ◽  
Special Issue

scholarly journals Receptor guanylyl cyclase (RGC) family (version 2020.3) in the IUPHAR/BPS Guide to Pharmacology Database

2020 ◽  
Vol 2020 (3) ◽  
Author(s):  
Annie Beuve ◽  
Peter Brouckaert ◽  
John C. Burnett, Jr. ◽  
Andreas Friebe ◽  
John Garthwaite ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Cyclic Gmp ◽  
Guanylyl Cyclase ◽  
Intestinal Epithelium ◽  
Mammalian Genome ◽  
Skeletal System ◽  
Diverse Range ◽  
Transmembrane Receptors ◽  
Retinal Photoreceptors ◽  
Grueneberg Ganglion

The mammalian genome encodes seven guanylyl cyclases, GC-A to GC-G, that are homodimeric transmembrane receptors activated by a diverse range of endogenous ligands. These enzymes convert guanosine-5'-triphosphate to the intracellular second messenger cyclic guanosine-3',5'-monophosphate (cyclic GMP). GC-A, GC-B and GC-C are expressed predominantly in the cardiovascular system, skeletal system and intestinal epithelium, respectively. GC-D and GC-G are found in the olfactory neuropepithelium and Grueneberg ganglion of rodents, respectively. GC-E and GC-F are expressed in retinal photoreceptors.

scholarly journals Base editing the mammalian genome

Methods ◽  
2019 ◽  
Vol 164-165 ◽  
pp. 100-108 ◽  
Author(s):  
Emma M. Schatoff ◽  
Maria Paz Zafra ◽  
Lukas E. Dow
Keyword(s):  
Mammalian Genome ◽  
Base Editing

scholarly journals Insertion of Foreign DNA into an Established Mammalian Genome Can Alter the Methylation of Cellular DNA Sequences

1999 ◽  
Vol 73 (2) ◽  
pp. 1010-1022 ◽  
Author(s):  
Ralph Remus ◽  
Christina Kämmer ◽  
Hilde Heller ◽  
Birgit Schmitz ◽  
Gudrun Schell ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Lines ◽  
Mammalian Genome ◽  
Dna Integration ◽  
Bhk21 Cell ◽  
Cellular Genes ◽  
Cell Clones ◽  
Dna Insertion ◽  
Foreign Dna ◽  
Methylation Patterns

ABSTRACT The insertion of adenovirus type 12 (Ad12) DNA into the hamster genome and the transformation of these cells by Ad12 can lead to marked alterations in the levels of DNA methylation in several cellular genes and DNA segments. Since such alterations in DNA methylation patterns are likely to affect the transcription patterns of cellular genes, it is conceivable that these changes have played a role in the generation or the maintenance of the Ad12-transformed phenotype. We have now isolated clonal BHK21 hamster cell lines that carry in their genomes bacteriophage λ and plasmid pSV2neo DNAs in an integrated state. Most of these cell lines contain one or multiple copies of integrated λ DNA, which often colocalize with the pSV2neo DNA, usually in a single chromosomal site as determined by the fluorescent in situ hybridization technique. In different cell lines, the loci of foreign DNA insertion are different. The inserted bacteriophage λ DNA frequently becomes de novo methylated. In some of the thus-generated hamster cell lines, the levels of DNA methylation in the retrotransposon genomes of the endogenous intracisternal A particles (IAP) are increased in comparison to those in the non-λ-DNA-transgenic BHK21 cell lines. These changes in the methylation patterns of the IAP subclone I (IAPI) segment have been documented by restriction analyses with methylation-sensitive restriction endonucleases followed by Southern transfer hybridization and phosphorimager quantitation. The results of genomic sequencing experiments using the bisulfite protocol yielded additional evidence for alterations in the patterns of DNA methylation in selected segments of the IAPI sequences. In these experiments, the nucleotide sequences in >330 PCR-generated cloned DNA molecules were determined. Upon prolonged cultivation of cell lines with altered cellular methylation patterns, these differences became less apparent, perhaps due to counterselection of the transgenic cells. The possibility existed that the hamster BHK21 cell genomes represent mosaics with respect to DNA methylation in the IAPI segment. Hence, some of the cells with the patterns observed after λ DNA integration might have existed prior to λ DNA integration and been selected by chance. A total of 66 individual BHK21 cell clones from the BHK21 cell stock have been recloned up to three times, and the DNAs of these cell populations have been analyzed for differences in IAPI methylation patterns. None have been found. These patterns are identical among the individual BHK21 cell clones and identical to the patterns of the originally used BHK21 cell line. Similar results have been obtained with nine clones isolated from BHK21 cells mock transfected by the Ca2+-phosphate precipitation procedure with DNA omitted from the transfection mixture. In four clonal sublines of nontransgenic control BHK21 cells, genomic sequencing of 335 PCR-generated clones by the bisulfite protocol revealed 5′-CG-3′ methylation levels in the IAPI segment that were comparable to those in the uncloned BHK21 cell line. We conclude that the observed changes in the DNA methylation patterns in BHK21 cells with integrated λ DNA are unlikely to preexist or to be caused by the transfection procedure. Our data support the interpretation that the insertion of foreign DNA into a preexisting mammalian genome can alter the cellular patterns of DNA methylation, perhaps via changes in chromatin structure. The cellular sites affected by and the extent of these changes could depend on the site and size of foreign DNA insertion.

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