PI in #Epigenetics. Fascinated by how stem cells work and how our genes make us. Can’t wait to find out what #citrullination is all about. Own views. She/her.
Cambridge, UK
Joined January 2020
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Our new #preprint by @phdanmoore has:
✅ A KRAB Zinc Finger (the SCAN domain-containing kind)
✅ #transposon sequences (the SINE kind)
✅ #epigenetic regulation (the #enhancer kind)
✅ lineage specification (the neural kind)
❌ and NO heterochromatin!
biorxiv.org/content/10.1101/…
Daniel drove and executed this work during his 4-year PhD. It's a bit difficult to convey how impressed I've been! 🚀🚀
So congratulations to him and thank you to our collaborators Eugenia Wong, @stefanschoenfe1, @mikhailspivakov and @simon_andrews.
It also suggests a molecular mechanisms that may underlie the genetic association between ZKSCAN3 and #schizophrenia.
Our work therefore identifies a #KZFP that regulates #enhancer function through targeting domesticated #transposon sequences and operates in a #heterochromatin independent manner.
Single cell RNA-seq after acute depletion of ZKSCAN3 during multi-lineage differentiation of ES cells shows that ZKSCAN3 operates during neural specification and mediates proper expression of dose-sensitive lineage commitment genes essential for wiring of the developing brain.
#KZFPs typically regulate through establishment of #heterochromatin, through interactions with KAP1/Trim28.
However:
- ZKSCAN3 doesn't bind KAP1
- ZKSCAN3 modulation does not affect H3K9me3
- The KRAB-deletion mutant rescues ZKSCAN3 function as well as the wild-type.
#KZFPs consist the largest family of transcription factors in most mammals and are well known for keeping #transposons in check.
Here, we found that ZKSCAN3 targets #enhancers containing 'domesticated' #transposons and suppresses their accessibility and function.
ZKSCAN3 belongs to a sub-family of #KZFPs that contain a poorly characterised SCAN domain. It is of particular interest as it exhibits strong genetic association with #schizophrenia risk.
In this work, Daniel genetically targeted mouse embryonic stem cells to knock in degron and epitope tags to the endogenous Zkscan3 locus.
This allowed him to manipulate and track this enigmatic #KZFP to understand its genomic localisation, mechanism of action and function.
Many congratulations Chien-Yun and team! Great to see this out.
🚀
Prosit-Cit is an important addition to the community’s toolkit for studying #citrullination
Kicking off the new year strong! 🚀
Prosit-Cit is officially online on MCP! Check it out: mcponline.org/article/S1535-…
Follow us on Bluesky for more exciting research updates! @ msleelab.bsky.social
Maria Christophorou retweeted
We are hiring! 3-year BBSRC-funded postdoc position available. TEs, epigenetics, pregnancy: if you love one or more of these keywords, apply through the link below. Please spread the word.
qmul-jobs.tal.net/vx/mobile-…
Thank you @J_Cell_Sci for giving us the opportunity to write this article. We thoroughly enjoyed it!
Fantastic proteins and where to find them – histones, in the nucleus and beyond
Johanna Grinat, Noah Shriever and @MAChristolab discuss the evolution & mechanisms of chromatin externalisation and (patho)physiological functions of extracellular histones.
journals.biologists.com/jcs/…
ALT Top image - A timeline of the evolution of histones, their complexing with chromatin, and other known or hypothesised functions. Histone proteins are represented as blue spheres. Archaeal histones mostly lack N-terminal tails and form a looser chromatin structure, whereas compaction is increased in simple and higher eukaryotes. Lower image - Modes of chromatin release throughout the tree of life. The slime mould Dictyostelium discoideum releases chromatin via ETosis only while in a multicellular ‘slug’ phase. Plants release chromatin via root extracellular traps for defence against pathogens, whereas animal cells carry out ETosis in many contexts, such as immune or inflammatory responses or tissue repair.
Maria Christophorou retweeted
Faculty jobs going in Cambridge Biochemistry!! Assistant Professor/Associate Professor in the area of Bioenergetics or Microbiology @Cambridge_Uni jobs.cam.ac.uk/job/49700/
This has been one of the most enjoyable pieces of work I have ever undertaken. There is something so wonderful about becoming immersed in academic work – reading, thinking, discussing, writing.
Thank you to @J_Cell_Sci for prompting us to put other things aside and focus on it!
With many thanks to @J_Cell_Sci, @Co_Biologists and @seemasainson for inviting us to write this article and congratulations to co-first authors, PhD student Noah Shriever and postdoc @JohannaGrinat.
journals.biologists.com/jcs/…
We drew knowledge and inspiration from the work of Arturo Zychlinsky, @VeniPap, @HarmitMalik, Steven Henikoff, @VashKurdistani, @KirmizisLab, Denisa Wagner, @kmartinod, Li Yang, @megeblad, Anne Brüstle and many others.