Project description:Annotation of small RNAs from 11 Drosophila species for the purpose of non-coding RNA annotation and comparative genomics assessment.
Project description:Sexual reproduction is nearly universal among multicellular animals, but sex can be determined by cues including sex chromosomes, temperature, social status, and photoperiod. DMRT transcription factors are key regulators of sex in animals that use diverse sex-determining strategies. These proteins are related to the sexual regulators Doublesex (Dsx) and Male abnormal-3 (MAB-3) of insects and nematodes, respectively. DMRT proteins share the DM DNA binding domain, comprised of a unique intertwined double zinc-binding module flanked by a C-terminal recognition helix that binds to a pseudopalindromic target DNA. Despite the central role of DMRT proteins in metazoan sexual development, how they recognize target DNA sequences is poorly understood. Here we find that DMRT proteins employ multiple DNA binding modes due to surprising versatility in how specific base contacts are made. Human DMRT1 can bind as a dimer, trimer or tetramer, in each case using paired antiparallel recognition helices that together insert into a widened DNA major groove to make base-specific contacts. Insertion of two helices in a single major groove is, to our knowledge, a DNA binding interaction unique to DMRT proteins. High resolution in vivo DNA binding analysis (ChIP-Exo) indicates that multiple DNA binding modes also are used in the mouse testis. Finally, we show that mutations affecting amino acid residues crucial for DNA recognition are associated with sex reversal in flies and also, for the first time, with male-to-female sex reversal in humans. Our results illuminate an ancient molecular interaction that underlies much of metazoan sexual development.
Project description:Curration of small RNAs from four melanogaster-subgroup species (Drosophila simulans, Drosophila sechellia, Drosophila erecta, and Drosophila yakuba) for the purpose of non-coding RNA annotation and comparative genomics assessment.
2014-07-22 | GSE56244 | GEO
Project description:ARCAD-Comparative population genomics
Project description:Comparative genomics studies in primates are extremely restricted due to our limited access to samples from non-human apes. In order to gain better insight into the genetic processes that underlie variation in complex phenotypes in primates, we must have access to faithful model systems for a wide range of cell types. To facilitate this, we have generated a panel of 7 fully characterized chimpanzee induced pluripotent stem cell (iPSC) lines derived from healthy donors. To begin demonstrating the utility of comparative iPSC panels, we collected RNA-sequencing and DNA methylation data from the chimpanzee iPSCs and the corresponding fibroblast lines, as well as from 7 human iPSCs and their source lines, which encompass multiple populations and cell types. We observe much less within-species variation in iPSCs than in somatic cells, indicating that the reprogramming process erases many inter-individual differences. The low within-species regulatory variation in iPSCs allowed us to identify many novel inter-species regulatory differences of small magnitude. We used ChIP-seq to characterize the genome-wide distribution of two types of histone modifications (H3K27me3 and H3K27ac) in three of our chimpanzee iPSCs and compared them to histone modification data from three human iPSC lines from the Roadmap Epigenomics project:
Project description:The largest and most diverse class of eukaryotic transcription factors contain Cys2-His2 zinc fingers (C2H2-ZFs). Here, we have explored the diversity of sequence preferences of C2H2-ZF proteins in non-metazoan organisms using PBM experiments.
