seanamontgomery.bsky.social
Postdoc in the Sebé-Pedrós lab at the CRG studying heterochromatin diversity and function across eukaryotes. Can be found chasing frisbees when not in the lab.
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🧵 reprise: our paper on protein network evolution in the piRNA genome defence pathway has now been published at @embojournal.org 🥳
Very positive experience with fast and constructive reviewing (thank you, three secret people) and good journal communication.
bsky.app/profile/embo...
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Or a postdoc in the lab of one of the organizers ;)
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Congrats James, it's great to see the final form at last! Definitely agree that 4mC could act as an imprinting mark at fertilization, would be amazing if someone could find the reader!
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Since people should see and appreciate your artwork!
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Many thanks to our collaborators Julen Mendieta and David Lara-Astiaso, and to the rest of the Sebé-Pedrós lab for their ongoing support! 12/12
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We hypothesize that the evolutionary arms race between TEs and their repression (and co-option) by host genomes helps drive diversity. But a missing component is the readers of these histone modifications and their downstream interactors, which I aim to address during the rest of my postdoc! 11/n
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My favourite example is from the chytrid fungus S. punctatus, which has a near perfect colocalization of H3K9me3 and H3K27me3 encompassing both TEs and genes (reminiscent of the effect of the dual writing ability of Ezl1 in ciliates) 10/n
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However, the more we look outside of animals and flowering plants (and the deeper we look at these species!), the more “exceptions” we find! 9/n
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Dearest to me is the diversity of histone modification combinations found in repressed heterochromatin. Traditionally, constitutive heterochromatin on transposable elements was defined by H3K9 methylation, and facultative heterochromatin on silent genes was defined by H3K27me3. 8/n
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(Here I went down a bit of a literature rabbit hole trying to understand how this could happen, but thanks to some great work in the trypanosome T. brucei, we hypothesize that the sub- and neofunctionalization of Dot1 homologs may be the key!) 7.5/n
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H3K79 methylation is written by a single enzyme, DOT1, and is associated with active gene bodies in fungi and animals. Surprisingly, while we saw dimethylation positively correlated with gene expression in the amoebazoan A. castellanii, trimethylation was negatively correlated! 7/n
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Histone acetylation associated with genes is typically restricted to active gene TSSs, but in three distantly related species, an ichthyosporean, a chytrid fungus, and a flowering plant, we saw elevated levels of histone acetylation along the length of inactive or lowly expressed genes. 6/n
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In line with previous observations, histone modifications associated with active genes are conserved, though some some interesting exceptions exist, specifically regarding broad histone acetylation domains and H3K79 methylation. 5/n
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My lucky role was to play with the vast wealth of data! To start, we defined 19 metastates, similar ChromHMM chromatin states that represented distinct combinations of chromatin marks. We believe this can serve as a useful framework to directly compare chromatin landscapes across species. 4/n
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To this end, iChIP2 was developed to generate the breadth of data needed to gain insights from all major eukaryotic lineages (see thread by @crisnava.bsky.social). She put in an immense effort generating all of the data, and even more optimizing the method and testing antibodies! 3/n
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While histone post-translational modifications are conserved across eukaryotes (see rdcu.be/eeaLN from @xgrau.bsky.social and @crisnava.bsky.social in our lab), we don’t know if they all play the same functional role. The first step is knowing where along the genome the modifications are found. 2/n