🐭🧬Our paper on locus-specific mouse L1 activity and regulation, led by the indomitable @Patricia_Grds is out @genomeresearch!🧬🐭. This study evolved from a simple question: what defines the mutagenic potential of a new L1 copy in vivo?. A thread:.1/n

Renee will represent @materresearch, @UQmedicine, and #mobileDNA enthusiasts everywhere at the University final later this year! #scicomm #3MT.

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Congratulations to multi-talented PhD student Renee Chu, who won the overall competition AND People’s Choice at the @UQmedicine 3MT final, using a thoughtful analogy to describe her research on jumping genes in early development 🧬🧫

RT @gabriela_bodea: The impact of LINE-1 retrotransposons on neurobiology is not fully understood. Our new research in @NatureNeuro sheds l….

RT @FranciscoJSL2: The Andalusian Government (south Spain) has opened a call for 3-year postdoctoral positions. If you would like to join m….

RT @CellGenomics: Locus-level L1 DNA methylation profiling reveals the epigenetic and transcriptional interplay between L1s and their integ….

RT @AEpiA: Interested in L1 retrotransposon regulation in development? . Check out AEpiA member @RichardsonL1Lab's recent paper in @genomer….

RT @manvendr7: Illuminating talk by @RichardsonL1Lab . Transcriptional regulation of Heritable activity of L1 activity in preimplantation e….

This study represents a huge amount of work by @Patricia_Grds, @Faulkner_Lab, and the most wonderful group of co-authors you could ask for: @Dory_genome, @MischaLundberg, @FranciscoJSL2, @gabriela_bodea, @_adamewing. 💗 and gratitude to all involved!. 20/20.

Together, our results suggest an interplay between L1 transcription initiation and de novo DNA methylation during differentiation in the early embryo, potentially involving YY1 or its binding sites within the L1 5’UTR. Excited to gain mechanistic insight into this process!. 19/n.

This also is likely to be true in humans, as somatic L1 insertions in the human brain frequently bear 5’ transductions consistent with upstream TSS usage. 18/n.

Finally, we observed that in day 21 differentiated cells where the L1 5’UTR is hypermethylated, upstream TSS usage becomes increasingly prevalent. Thus, individual mouse L1 loci positioned downstream of genomic promoters may be privileged for retrotransposition in the soma. 17/n

The mouse L1 TSS pattern is consistent with the above study from the Kazazian lab, and also with work from John Moran’s lab demonstrating that a YY1 binding site is required for accurate human L1 transcription initiation. 16/n.

Analysing uniquely mapping 5’RACE reads alongside composite DNA methylation profiles, we found that like the peaks in DNA methylation, L1 TSSs also clustered around the YY1 binding sites. 15/n

We next investigated the relationship between L1 5’UTR methylation and transcription start site (TSS) selection. We combined 5’RACE with PacBio SMRT sequencing in an approach similar to that of Prescott Deininger and @BelancioLab for human L1. 14/n.

The peaks in methylation flank binding sites for the transcription factor YY1 (red). Notably, our previous study led by @FranciscoJSL2 demonstrated that the YY1 transcription factor, or its binding site, is important for human L1 DNA methylation. 13/n

Intriguingly, we observed a “smile” pattern in DNA methylation across the 5’UTR, suggesting that 5’UTR methylation proceeds in an outside-in fashion during differentiation. What’s more, the smile was not smooth but “toothy”, with peaks and valleys. 12/n

By plotting CpG methylation across full-length L1s, we found that the mouse L1 body is hypermethylated even in mESCs, while methylation of the 5’UTR is dynamic during differentiation. 11/n

We applied ONT analysis to query L1 DNA methylation genome-wide with locus resolution in mESCs and EBs at day 3 and day 21 of differentiation. These results nicely corroborated our findings with locus-specific bis-seq, and offered several novel observations:. 10/n

We therefore collaborated with @_adamewing , who developed and applied software packages TL;DR and Methylartist to examine the methylation state of human L1 insertions using ONT long-read DNA sequencing data. 9/n.

Locus-specific bisulfite sequencing is limited in that L1s need to be queried one-by-one with specifically designed primers, and bisulfite treatment fragments DNA and makes it impossible to analyse DNA methylation across a ~7kb L1, or even across the whole 5’UTR promoter. 8/n.