Comprehensive analysis of the chromatin landscape in Drosophila melanogaster.

Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function

Comparison of dot chromosome sequences from D. melanogaster and D. virilis reveals an enrichment of DNA transposon sequences in heterochromatic domains

BACKGROUND: Chromosome four of Drosophila melanogaster, known as the dot chromosome, is largely heterochromatic, as shown by immunofluorescent staining with antibodies to heterochromatin protein 1 (HP1) and histone H3K9me. In contrast, the absence of HP1 and H3K9me from the dot chromosome in D. virilis suggests that this region is euchromatic. D. virilis diverged from D. melanogaster 40 to 60 million years ago. RESULTS: Here we describe finished sequencing and analysis of 11 fosmids hybridizing to the dot chromosome of D. virilis (372,650 base-pairs) and seven fosmids from major euchromatic chromosome arms (273,110 base-pairs). Most genes from the dot chromosome of D. melanogaster remain on the dot chromosome in D. virilis, but many inversions have occurred. The dot chromosomes of both species are similar to the major chromosome arms in gene density and coding density, but the dot chromosome genes of both species have larger introns. The D. virilis dot chromosome fosmids have a high repeat density (22.8%), similar to homologous regions of D. melanogaster (26.5%). There are, however, major differences in the representation of repetitive elements. Remnants of DNA transposons make up only 6.3% of the D. virilis dot chromosome fosmids, but 18.4% of the homologous regions from D. melanogaster; DINE-1 and 1360 elements are particularly enriched in D. melanogaster. Euchromatic domains on the major chromosomes in both species have very few DNA transposons (less than 0.4 %). CONCLUSION: Combining these results with recent findings about RNAi, we suggest that specific repetitive elements, as well as density, play a role in determining higher-order chromatin packaging

A High-Resolution Whole-Genome Map of Key Chromatin Modifications in the Adult Drosophila melanogaster

Epigenetic research has been focused on cell-type-specific regulation; less is known about common features of epigenetic programming shared by diverse cell types within an organism. Here, we report a modified method for chromatin immunoprecipitation and deep sequencing (ChIP–Seq) and its use to construct a high-resolution map of the Drosophila melanogaster key histone marks, heterochromatin protein 1a (HP1a) and RNA polymerase II (polII). These factors are mapped at 50-bp resolution genome-wide and at 5-bp resolution for regulatory sequences of genes, which reveals fundamental features of chromatin modification landscape shared by major adult Drosophila cell types: the enrichment of both heterochromatic and euchromatic marks in transposons and repetitive sequences, the accumulation of HP1a at transcription start sites with stalled polII, the signatures of histone code and polII level/position around the transcriptional start sites that predict both the mRNA level and functionality of genes, and the enrichment of elongating polII within exons at splicing junctions. These features, likely conserved among diverse epigenomes, reveal general strategies for chromatin modifications

Engaging Biologists with Big Data Using Interactive Genome Annotation

<p>Poster for November 2015 BD2K meeting.</p

Building Back More Equitable STEM Education: Teach Science by Engaging Students in Doing Science

The COVID-19 pandemic is a national tragedy, one that has focused our attention on both the need to improve science education and the need to confront systemic racism in our country. We know that active learning strategies, in particular research experiences, can engage and empower STEM undergraduates, effectively closing the achievement gap for historically excluded persons. The apprenticeship model for STEM training – supervised research under a dedicated mentor – is highly effective, but out of reach for most students. Recent efforts have demonstrated that Course-based Undergraduate Research Experiences (CUREs) can be an effective approach for making STEM research accessible for all. Our meta-analysis of CUREs finds that published examples now cover the breadth of the typical undergraduate biology curriculum. A thoughtfully designed CURE can go beyond foundational knowledge and analytical thinking to include career-related skills, e.g., teamwork and communication. Similarly, it can be designed with equity as a foundational principle, taking into account the unique contributions of all students and their varying needs. We provide here an example framework (The “Do Science Framework”) for making STEM training more effective and inclusive using CUREs. While CUREs do not inherently address equity, there can be no equity in STEM education without equal access to research participation, and progress toward this goal can be achieved using CUREs. However, implementing new CUREs is not a trivial undertaking, particularly at schools with high teaching loads and little or no research infrastructure, including many community colleges. We therefore propose a National Center for Science Engagement to support this transition, building on experiences of current nationally established CUREs as well as the work of many individual faculty. In the aftermath of the COVID-19 pandemic, academia has a renewed responsibility to dismantle structural inequities in education; engaging all STEM students in research can be a key step

Insights from a Convocation: Integrating Discovery-Based Research into the Undergraduate Curriculum.

The National Academies of Sciences, Engineering, and Medicine organized a convocation in 2015 to explore and elucidate opportunities, barriers, and realities of course-based undergraduate research experiences, known as CUREs, as a potentially integral component of undergraduate science, technology, engineering, and mathematics education. This paper summarizes the convocation and resulting report