Project description:Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss of function variants in desmosomal genes lead to a variety of skin and heart related phenotypes. Here, we report tuftelin 1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair and mild palmoplantar keratoderma, but without a cardiac phenotype, we identified a homozygous splice site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of tuftelin 1 protein. Patients’ skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that tuftelin 1 is positioned within the desmosome and its location dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1 knock-out mouse model mimicked the patients’ phenotypes. Altogether, this study reveals tuftelin 1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair and palmoplantar keratoderma.
Project description:Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides, and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) which died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding twenty-eight chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive-X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth’s death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.
Project description:We report the sequences bound to CENP-A in the dog genome (Canis familiaris) for high-throughput characterization of centromeric sequences. We compare these ChIPSeq reads (72 bp, single read) against a reference centromeric satellite DNA domain database for the dog genome, resulting in the annotation of sequence variation and estimated abundance of seven satellite families together with adjacent, non-satellite sequences. To study global patterns of sequence diversity and characterizing the subset of sequences correlated with centromere function, these sequences were evaluated relative to a comprehensive centromere sequence domain k-mer library. From this analysis, we identify functional sequence features from two satellite families (CarSat1 and CarSat2) that are defined by distinct arrays subtypes.
Project description:We report the sequences bound to CENP-A in the dog genome (Canis familiaris) for high-throughput characterization of centromeric sequences. We compare these ChIPSeq reads (72 bp, single read) against a reference centromeric satellite DNA domain database for the dog genome, resulting in the annotation of sequence variation and estimated abundance of seven satellite families together with adjacent, non-satellite sequences. To study global patterns of sequence diversity and characterizing the subset of sequences correlated with centromere function, these sequences were evaluated relative to a comprehensive centromere sequence domain k-mer library. From this analysis, we identify functional sequence features from two satellite families (CarSat1 and CarSat2) that are defined by distinct arrays subtypes. Sequences bound to CENP-A in MDCK (dog) cell line
Project description:The 28,000-year-old remains of a woolly mammoth, named ‘Yuka’, were found in Siberian permafrost. We performed proteomic analyses of muscle and bone marrow samples obtained from the remains to gain information about the repertoire and modifications of proteins.
Project description:With a view to re-annotate the genome sequence of the nitrogen fixing bacterium Sinorhizobium meliloti, we generated oriented sequences of transcripts. To cover a large number of expressed genes we prepared RNA from bacteria grown in three very different physiological conditions including bacteria grown in liquid cultures (in both exponential and stationary growth phases) and from 10-day-old nodules in which bacteria were differentiated in nitrogen fixing bacteroids. The transcripts sequences were then integrated into EuGene-P, a new prokaryotic genome annotation tool able to integrate high throughput data including oriented RNA-Seq data directly into the prediction process, which led to the production of an accurate and complete annotation of the genome of S. meliloti strain 2011.
