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Dominik Handler @86dominik.bsky.social · 18d

No problem at all! I'm happy to clarify any questions that arise.

Dominik Handler @86dominik.bsky.social · 18d

We used the term in this thread to distinguish this assembly from contig-only assemblies. If the usage of 'chromosome-scale' was misleading, we apologize, there was no intent to mislead.

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Dominik Handler @86dominik.bsky.social · 18d

We referred to it as chromosome scale as it is assembled into chromosome-level scaffolds spanning entire chromosome arms. We clearly state in the text that it is not telomere-to-telomere (T2T) and does not fully resolve highly repetitive loci like rDNA arrays or centromeres.

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Dominik Handler @86dominik.bsky.social · 18d

Thank you Jakob 😃.

Dominik Handler @86dominik.bsky.social · 19d

Finally, huge thanks to @juliusbrennecke.bsky.social and the whole Brennecke Group for enduring my long-read obsession! Also worth noting: the Iwasaki and Siomi labs recently published an OSC genome assembly (PMID: 39636727). Exciting to see multiple groups tackling this important resource. (12/12🏁)

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Dominik Handler @86dominik.bsky.social · 19d

Many questions remain about how these patterns emerge and how the right piRNA precursors are selected, but that's a story for another day ;-).
For now, check out the story and explore the genome yourself. We'd love to get your feedback! (11/12)
www.biorxiv.org/content/10.1...

The Drosophila OSC Genome: A Resource for Studies of Transposon and piRNA Biology

Accurate genome assemblies are critical for understanding small RNA-mediated genome defense. In animals, the PIWI-interacting RNA (piRNA) pathway protects genome integrity by silencing transposable el...

www.biorxiv.org

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Dominik Handler @86dominik.bsky.social · 19d

Together, these advances let us explain transposon silencing patterns genome-wide. Cluster content determines piRNA profiles, which in turn dictate which TEs are silenced and which evade the pathway. (10/12)

Small RNA coverage and piRNA cluster representation across the mdg1 retrotransposon. Top tracks show mdg1 fragments embedded in somatic piRNA clusters for dm6 (sense in blue, antisense in orange) and OSC-r1.01 genomes. Below, small RNA patterns observed in OSCs are shown across the mdg1 element. The overall very close fit between the cluster-contained fragments in the OSC genome and the piRNA patterns suggests the accuracy of the assembly.

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Dominik Handler @86dominik.bsky.social · 19d

Earlier work suggested flamenco undergoes splicing. Our data shows that beyond the first intron, the >730 kb transcript appears to be largely unspliced, producing a single continuous precursor feeding the piRNA pathway. (9/12)

Splice junction usage at the Dip1-flamenco locus. Schematic showing the Dip1 gene (orange, left) adjacent to the flamenco piRNA cluster (blue arrow, right). Arc diagram displays splice junctions connecting exons, with dark red arcs indicating high-efficiency splice junctions (>5% usage) and gray arcs showing low-efficiency junctions (<5%). Multiple high-efficiency splice junctions are present within Dip1, while long-range connections extending across the flamenco region (spanning >20 kb) show predominantly low efficiency. This pattern suggests that while Dip1 undergoes conventional splicing, the flamenco locus produces predominantly unspliced or inefficiently spliced transcripts.

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Dominik Handler @86dominik.bsky.social · 19d

Next challenge: determining flamenco's transcriptional extent. We inserted UAS sites upstream and tethered a silencing domain to reduce transcription. The result? piRNA loss extending ≥730 kb downstream, revealing the true scale of this massive locus. (8/12)

Tethering assay demonstrates long-range silencing from the flamenco piRNA cluster. Top: Experimental design showing transient expression of Gal4-Panoramix IDR silencing domain, which binds to a homozygous 14x UAS array insertion upstream of flamenco. Bottom: Scatter plot showing fold change in gene expression upon IDR tethering across a 750 kb region surrounding flamenco. The flamenco locus shows strong silencing (>2-fold repression). The upstream and downstream regions shows minimal effect. This demonstrates that tethering the Panoramix silencing domain to flamenco induces specific silencing of flamenco that extends over >700kb.

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Dominik Handler @86dominik.bsky.social · 19d

So how are these TEs controlled? The flamenco piRNA cluster, OSCs' primary piRNA source, is critical. We resolved the entire locus, bridging an assembly gap in dm6 and it differs not just by a few SNPs: we see major rearrangements and dramatic content changes throughout the locus. (7/12)

Structural variant relationships between OSC-r1.01 and dm6 genomes at the flamenco locus. Ribbon diagram showing syntenic regions (gray), translocations (teal), and duplications (blue) across the ~700 kb flamenco piRNA cluster region. The OSC-r1.01 assembly (top) is compared to dm6 (bottom), with connecting ribbons indicating homologous relationships. The complex pattern of translocations and duplications, particularly concentrated in the 200-500 kb region, reflects extensive structural rearrangement at this critical piRNA-producing locus.

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Dominik Handler @86dominik.bsky.social · 19d

How dramatically? OSCs harbor >150 gypsy retrovirus insertions (dm6 has one), while tirant (present in dm6) is absent from OSCs. These post-immortalization changes fundamentally reshape transposon-piRNA dynamics. (6/12)

Distribution of transposable element families in genome-exclusive structural variants. Horizontal bar chart showing the count of large (>1000 nt) transposable element-containing structural variants that are exclusive to either dm6 (orange bars, extending left) or OSC (dark blue bars, extending right). Transposon families are ranked by total abundance, with springer, gypsy, and copia showing the highest counts of OSC-exclusive insertions. The roo element shows substantial dm6-exclusive presence. Most TE families display asymmetric distribution, with OSC harboring more exclusive insertions for the majority of families, reflecting transposon mobilization during cell line establishment.

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Dominik Handler @86dominik.bsky.social · 19d

OSCs show extensive loss-of-heterozygosity regions from events during immortalization as shown previously by @caseybergman.bsky.social (PMID: 34849875) The transposon landscape? It evolved after these LOH events—meaning the insertions we see reflect post-immortalization genome dynamics. (5/12)

Chromosome-wide distribution of SNPs and structural variants in the OSC genome. Three-row panel showing allele frequency patterns across all major chromosomes (2L, 2R, 3L, 3R, 4, X). Top row: SNP density plots show high-density regions (dark bands) concentrated in specific chromosomal regions, particularly on 2L, 3L, and 3R, with chromosomes 2R and X showing sparser SNP distribution due to loss of heterozygosity. Middle row: Short indel allele frequencies (red dots) are distributed across all chromosomes, with blue dots highlighting transposable element-containing structural variants that cluster in specific regions. Bottom row: Large structural variant allele frequencies (black dots) show concentrated clustering, particularly on chromosomes 3L and 3R, with transposable element-containing SVs (red dots) distributed throughout. The patterns reveal heterogeneous genomic architecture with chromosome-specific variation landscapes, reflecting the complex evolutionary history of the OSC cell line including loss-of-heterozygosity events and transposon mobilization.

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Dominik Handler @86dominik.bsky.social · 19d

Ready to explore? The assembly is live on UCSC Genome Browser with our functional datasets integrated: ChIP-seq, RNA-seq, PRO-seq, and small RNA-seq. Fully annotated and ready for you to go bird watching. (4/12)
genome-euro.ucsc.edu/s/Brennecke%...

Genome browser view of the Myc-RA locus including data-tracks. The gene structure (top, blue) includes the 3' UTR end determined by direct RNA sequencing (red arrowhead). Tracks show regulatory activity (STARR-seq), chromatin accessibility (DHSseq), nascent transcription (PRO-seq), gene expression (RNA-seq), small RNA production (sRNA-seq), and chromatin marks (Pol II and H3K9me3 ChIP-seq) under control (siLuc) and Piwi knockdown (siPiwi) conditions.

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Dominik Handler @86dominik.bsky.social · 19d

Using Oxford Nanopore long reads + Hi-C scaffolding, we generated a chromosome-scale assembly with superior contiguity to dm6 and corrected nearly all those fixed variants, capturing the true OSC genomic sequence. (3/12)

Dot plot comparing the OSC-r1.01 genome assembly to the dm6 reference genome. The plot shows chromosome-level synteny between the OSC cell line genome (y-axis) and the Drosophila melanogaster reference genome dm6 (x-axis). The diagonal blue line represents collinear regions of unique sequence (blue dots), while orange dots indicate repetitive sequences, predominantly transposable elements. Major chromosomes are labeled (2L, 2R, 3L, 3R, 4, X). The strong diagonal signal demonstrates overall chromosomal synteny between OSC and dm6.

Comparison of genetic variation between dm6 reference and OSC-r1.01 genomes. Two bar charts show (left) SNPs plus short variants and (right) structural variants, categorized by zygosity. Black bars represent homozygous variants; orange bars represent heterozygous variants. The dm6 reference shows ~560,000 homozygous and ~265,000 heterozygous SNPs/short variants, with ~4,000 homozygous and ~3,250 heterozygous structural variants. In contrast, OSC-r1.01 displays dramatically reduced homozygous variation (~5,000 SNPs/short variants and ~100 structural variants) but similar heterozygous variation (~275,000 SNPs/short variants and ~3,600 structural variants). This pattern reflects the improved accuracy of the phased OSC-r1.01 assembly in capturing the true genomic content of the OSC cell line.

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Dominik Handler @86dominik.bsky.social · 19d

OSCs are widely used for transposon silencing and piRNA studies, but everyone's been mapping to dm6. The problem? OSCs differ by >500K homozygous SNPs and >4,000 structural variants. Try designing siRNAs against SoYb when the reference has 85 homozygous differences in its CDS alone. (2/12)

$Bar chart comparing structural variations (SVs) between the dm6 reference genome and OSC genome assembly. The left bar shows all SVs (~5,300 total), with approximately 3,300 OSC-exclusive variants (black) and 2,000 dm6-exclusive variants (yellow/gold). The right bar displays SVs with >80% transposable element (TE) content (~2,700 total), with approximately 1,900 OSC-exclusive and 800 dm6-exclusive TE-associated variants. This demonstrates that OSCs contain substantially more unique structural variants than the reference genome, with TEs accounting for a major fraction of genomic differences—consistent with transposon mobilization during cell line immortalization.$

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Dominik Handler @86dominik.bsky.social · 19d

When transposons jump, genomes diverge - even in cultured cells.
I am happy to share our new preprint: a chromosome-scale genome assembly for Drosophila OSC cells, one of the key model systems in the piRNA field, especially for nuclear piRNA biology. 🧬🧵 (1/12)

Graphical abstract: The Drosophila OSC Genome as a resource for transposon and piRNA biology. The figure illustrates the workflow and key findings. Left: De novo genome assembly using Oxford Nanopore Technologies (ONT) long reads and Hi-C data generates a phased assembly distinguishing unique (blue) and repetitive (orange) sequences. Dot plot comparison between OSC-r1.01 and dm6 reference genomes shows overall synteny with extensive structural variation. Middle: A freely accessible UCSC genome browser session displays multi-omics data tracks including gene models, transposon insertions, chromatin accessibility, transcription, small RNAs, and histone modifications. Right: New insights into flamenco piRNA cluster biology reveal >730 kb transcribed from a single promoter without major splicing. Tethering assays demonstrate long-range silencing effects across the locus, and genome browser tracks show coordinated regulation of piRNA production, transcription, and chromatin state. This resource enables comprehensive studies of transposon regulation and piRNA pathway function in a widely-used Drosophila cell line.

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Reposted by Dominik Handler

Julius Brennecke @juliusbrennecke.bsky.social · 21d

Off he is ...

Ulrich is one of the most remarkable scientists I had the pleasure to work with. I learned so much from him about biochemistry, proteins, structural biology, and so much more.

Great people make great things happen.
The really great people are rare.
Ulrich is one of them ...

Ulrich Hohmann @hohmannulrich.bsky.social · 21d

Thrilled to share that I’ll be joining @imbmainz.bsky.social in February 2026 to start my own group!
We will explore new mechanisms in eukaryotic gene expression, leveraging ‘evolutionary play’ to uncover how regulation, repurposing, and hijacking shape RNA biology.
PhD positions available!

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Reposted by Dominik Handler

Ulrich Hohmann @hohmannulrich.bsky.social · 21d

Thrilled to share that I’ll be joining @imbmainz.bsky.social in February 2026 to start my own group!
We will explore new mechanisms in eukaryotic gene expression, leveraging ‘evolutionary play’ to uncover how regulation, repurposing, and hijacking shape RNA biology.
PhD positions available!

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Dominik Handler @86dominik.bsky.social · Aug 21

📌

Reposted by Dominik Handler

Baptiste Rafanel @baptisterafanel.bsky.social · Aug 14

1/ How do animals develop immunity against a newly encountered transposable element from scratch? Our study reveals that the mobility of TEs is their Achilles heel, allowing hosts to develop a powerful small RNA-mediated silencing response.
www.biorxiv.org/content/10.1...

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Reposted by Dominik Handler

Julius Brennecke @juliusbrennecke.bsky.social · Aug 3

piRNAs are essential for transposon silencing in the animal germline.
But how do hosts trap transposon sequences in genomic loci that help establish a piRNA response?

Looking at a natural transposon invasion, Baptiste Rafanel and Kirsten Senti made some remarkable observations.

bioRxiv Genetics @biorxiv-genetic.bsky.social · Aug 1

Antisense transposon insertions into host genes trigger piRNA mediated immunity https://www.biorxiv.org/content/10.1101/2025.07.28.667215v1

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Reposted by Dominik Handler

Institute of Molecular Biotechnology @imbavienna.bsky.social · May 12

Kristina Stapornwongkul and Sven Klumpe are new IMBA Group Leaders starting in 2025. Who will join IMBA in 2026? IMBA is hiring a Junior Group Leader. Apply to the position by May 18: imba.science/beagroupleader #hiring #biology #research #groupleader #europe

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Reposted by Dominik Handler

Julius Brennecke @juliusbrennecke.bsky.social · Mar 29

We are seeking a new colleague to join us at the Vienna BioCenter, specifically at my beloved home institution, IMBA @imbavienna.bsky.social

we value collegiality and a passion for curiosity driven science. Being a great and fun human being also helps!

Institute of Molecular Biotechnology @imbavienna.bsky.social · Mar 28

IMBA is recruiting a Junior Group Leader! Are you interested in starting your own lab, pursuing curiosity-driven basic research in the life sciences? Apply now to our group leader position. The deadline is May 28. Link is below.

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Reposted by Dominik Handler

Maya Voichek @mayavoichek.bsky.social · Mar 17

1/ Transposable elements are often called "jumping genes" because they mobilize within genomes. 🧬
But did you know they can also jump 𝘣𝘦𝘵𝘸𝘦𝘦𝘯 cells? 🤯
Our new study reveals how retrotransposons invade the germline directly from somatic cells.
www.biorxiv.org/content/10.1...
A short thread 🧵👇

Drosophila follicle showing retrotransposons (pink & yellow) expressed in somatic cells infecting the oocyte

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Reposted by Dominik Handler

Sven Klumpe @svenklumpe.bsky.social · Mar 5

Happy to share our manuscript on the in situ visualization of the copia retrotransposon in its final form today published in @cellcellpress.bsky.social www.cell.com/cell/fulltex.... What’s new?

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