For the those in Edinburgh, tonight is the 10th anniversary meeting of the Edinburgh Chromatin, #epigenetics and transcription network (now on bluseky: @edinepigenetics.bsky.social). Do go along to hear some great science. Sad to be missing it due to illness and lack of childcare 😢

For those of you in Edinburgh, tree down this morning on the cycle path between Canonmills and Trinity (I think route 13). Have attempted to report to the council. @spokes.org.uk

We then asked what might cause this relocalisation of DNMT3A. Using ChIP-seq we found that hypermethylated PMDs lost H3K9me3 and gained H3K36me2 suggesting this change in chromatin state enabled DNMT3A recruitment. 🧵 6/8

Instead we thought the gains in methylation might be caused by another DNMT. We found that DNMT3A but not DNMT3B localised to hypermethylated PMDs suggesting that this was indeed the case. 🧵 5/8

We therefore wondered why this might have occurred. Despite the links between hypomethylation and late replication, we found that these hypermethylated PMDs remained late replicating using repli-seq. 🧵 4/8

We therefore asked what happened to PMDs in DNMT1 KO colorectal cancer cells. We observed a bias towards losses of DNA methylation from PMDs. However, very surprisingly, we also saw that around 10% of H3K9me3-marked PMDs gained methylation in DNMT1 KO cells! 😮😮😮🧵 3/8

Interested in a #postdoc in Edinburgh working on #interdisciplinary #epigenetics and having this view on your morning commute? Upcoming opportunities to apply for funding below 🧵 1/3. Get in touch if you are interested.

Congratulations to Andreanna (now Dr Wright) from the lab on her successful PhD defence yesterday 🥳. Thanks to Kevin Myant and Adele Murrell who were kind enough to act as examiners.

We propose DNMT3B is recruited to and methylates H3K9me3-marked heterochromatin facilitated by its N-terminal region and HP1. Hypermethylation of heterochromatin in the case of PWWP mutations results from the redistribution of DNMT3B away from H3K36me3.
🧵 7/9

We show that this interaction with HP1 is direct and that DNMT3B's N-terminal region is necessary and sufficient to interact with HP1. Furthermore, HP1 increases DNMT3B's affinity for H3K9me3 nucleosomes in an EMSA in vitro. 🧵 6/9

The biggest addition is elaboration of the molecular mechanism responsible for DNMT3B activity at H3K9me3 marked heterochromatin. We show that DNMT3B can pull down HP1 and H3K9me3 from cells in an N-terminus dependent manner. 🧵 5/9

We've also confirmed that PWWP mutations cause hypermethylation of heterochromatin in an independent cell line. 🧵 4/9

In the revised version we have utilised catalytic dead PWWP mutant DNMT3B to demonstrate DNMT3B's catalytic activity is required for this hypermethylation. 🧵 3/9

We previously analysed DNMT3B knockout cells showing that they lose methylation from H3K9me3-marked heterochromatin and that mutation of DNMT3B's PWWP results in hypermethylation of heterochromatin. 🧵 2/9

Our institute is looking for a new Bioinformatics Analysis Core Manager. If you fancy working in the beautiful city of Edinburgh in a fantastic collegiate, collaborative research environment, do apply. #Bioinformatics
Deadline 17th Jan, details: elxw.fa.em3.oraclecloud.com/hcmUI/Candid...