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Genome Research Papers on Craniosynostosis, Macaque Retrotransposition, More

A team from Israel, Belgium, and other international centers examine structural variants involved in individuals with an autosomal dominant craniofacial and limb malformation condition known as craniosynostosis, focusing on SVs affecting regulatory elements. Using chromatin immunoprecipitation sequencing centered on several histone modifications in embryonic craniofacial tissue samples — combined with ChIP-seq, ATAC-seq, and other analyses on mouse embryonic models — the researchers narrowed in on HDAC9 SVs that altered TWIST1 regulatory elements, including enhancers linked to craniofacial development. "[W]e showed that SVs that affect the HDAC9 sequence can also modulate basic mechanisms of gene regulation controlling the expression of a nearby gene, TWIST1," they report. "These SVs affect TWIST1 regulatory elements and disrupt higher-order chromatin organization, leading to a phenotype that is not associated with the HDAC9 protein."

Investigators at the University of Queensland and other centers in Australia, France, Spain, and elsewhere track somatic retrotransposon LINE-1 (L1) activity in the rhesus macaque (Macaca mulatta) brain. With the help of single-cell whole-genome sequencing, retrotransposon capture sequencing, RNA sequencing, and other approaches, the team profiled 20 post-mortem hippocampal neurons from two adult male macaques, unearthing a PCR-validated L1 insertion in some 7 percent of the hippocampal neurons considered that was analyzed using available RNA sequence data. "The corresponding donor L1 allele was exceptionally mobile in vitro, and was embedded in PRDM4, a gene expressed throughout development and in neural stem cells," the authors write. "These data highlight endogenous macaque L1 retrotransposition potential, provide prototypical evidence of L1-mediated somatic mosaicism in a non-human primate, and allude to L1 mobility in the brain over the last 30 million years of human evolution."

A University of New South Wales-led team reports on findings from transcriptome analyses of a synchronized human glioblastoma cell line analyzed at 10 minute intervals for up to nearly seven hours, following the expression of more than 3,500 protein-coding genes and more than 2,800 long non-coding RNAs. The team went on to do validation experiments in mouse dendritic cells. Although they found synchronous lncRNA and nearby gene expression, the authors report that "broad-scale cis-regulatory roles for lncRNAs are not common." Consequently, they speculate that the lncRNA-neighboring gene ties may reflect "an origin as transcriptional by-products from active protein-coding gene promoters and enhancers."