scholarly journals Engineered miniature CRISPR-Cas system for mammalian genome regulation and editing

2021 ◽  
Author(s):  
Xiaoshu Xu ◽  
Augustine Chemparathy ◽  
Leiping Zeng ◽  
Hannah R. Kempton ◽  
Stephen Shang ◽  
...  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wendan Ren ◽  
Huitao Fan ◽  
Sara A. Grimm ◽  
Jae Jin Kim ◽  
Linhui Li ◽  
...  

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.


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

2020 ◽  
Vol 2020 (3) ◽  
Author(s):  
Annie Beuve ◽  
Peter Brouckaert ◽  
John C. Burnett, Jr. ◽  
Andreas Friebe ◽  
John Garthwaite ◽  
...  

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.


Author(s):  
Victor AO. Carmelo ◽  
Haja N. Kadarmideen

AbstractImprovement of feed efficiency (FE) is key for sustainability and cost reduction in pig production. Our aim was to characterize the muscle transcriptomic profiles in Danbred Duroc (Duroc) and Danbred Landrace (Landrace), in relation to FE for identifying potential biomarkers. RNA-seq data was analyzed employing differential gene expression methods, gene-gene interaction and network analysis, including pathway and functional analysis. We compared the results with genome regulation in human exercise data. In the differential expression analysis, 13 genes were differentially expressed, including: MRPS11, MTRF1, TRIM63, MGAT4A, KLH30. Based on a novel gene selection method, the divergent count, we performed pathway enrichment analysis. We found 5 significantly enriched pathways related to feed conversion ratio (FCR). These pathways were mainly mitochondrial, and summarized in the mitochondrial translation elongation (MTR) pathway. In the gene interaction analysis, highlights include the mitochondrial genes: PPIF, MRPL35, NDUFS4and the fat metabolism and obesity genes: AACS, SMPDL3B, CTNNBL1, NDUFS4 and LIMD2. In the network analysis, we identified two modules significantly correlated with FCR. Pathway enrichment of modules identified MTR, electron transport chain and DNA repair as enriched pathways. In the network analysis, the mitochondrial gene group NDUF was a key hub group, showing potential as biomarkers. Comparing with human transcriptomic exercise studies, genes related to exercise displayed enrichment in our FCR related genes. We conclude that mitochondrial activity is a driver for FCR in muscle tissue, and mitochondrial genes could be potential biomarkers for FCR in pigs. We hypothesize that increased FE mimics processes triggered in exercised muscle.


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