Thread by @NAltemose

More good news! Our paper describing DiMeLo-seq is now published in @naturemethods. DiMeLo-seq uses long-read sequencing to map specific protein-DNA interaction sites on single chromatin fibers, with lots of cool applications in epigenomics. 👇 nature.com/articles/s4159… /1

For a general overview, see our previous thread on the preprint (with accompanying Enrique Iglesias references):

https://twitter.com/NAltemose/status/1412831046614224900?s=20&t=VV-ArbtTHvoCk-pds1GAtw

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Since the preprint, we further improved the protocol, increasing methylation efficiency 50-60% without sacrificing specificity, and we showed that we can detect mA deposited in vivo by direct fusion of the target protein to a MTase (as in DamID/MadID) doi.org/10.17504/proto… /3

We demonstrated that DiMeLo-seq is compatible with PacBio sequencing, and we showed that DiMeLo-seq reads can be phased to reveal how haplotype-specific differences in DNA sequence and CpG methylation associate with protein-DNA interactions on single molecules. /4

Many thanks to our anonymous reviewers for their constructive feedback and to our editor @DrLeiTang for helping us get out the final version as quickly as possible to accompany the recent #T2T papers. A transparent review report accompanies the paper. /5

Thanks especially to our amazing team and supporters!
@NAltemose, @AnnieMaslan, @SmithOwenK, @KousikSun, @khmiga, @airstreets, @astraight, @czbiohub, @BerkeleyBioE, @berkeleyMCB, @StanfordBiochem, @HHMINEWS, @NIH, @NSF, @NIGMS, @genome_gov, #T2T /6

And of course thank you to all the engineers and scientists who laid the groundwork that made this technology possible: @nanopore, @PacBio, @Stoibs11, @bvansteensellab, @WJGreenleaf, @timp0, @vram142, @kind_jop, Stergachis Lab, Henikoff Lab, Au Lab & many others! /7

Recently, we’ve been collaborating to demonstrate DiMeLo-seq in primary tissues and in other model organisms. The first data back are from fly embryos and look great! /8

We’re eager to get DiMeLo-seq into labs everywhere. All of our plasmids are in @Addgene, our protocols are on @protocolsIO (linked above), and we’re happy to ship you some pA-Hia5 to get you started. Stay tuned for an analysis software package from the incredible @AmAslan! /9