Grace Bower

In new work by @jahn0.bsky.social and I in @jbloomlab.bsky.social, we investigate how sequence constraints differ across influenza HA subtypes.

We find ~50% of sites in HA display substantially different amino-acid preferences across H3, H5, and H7.

doi.org/10.64898/202...

Not that long ago, in vivo mouse enhancer design was a dream. Today, it's a reality! Using transfer deep learning to design de novo synthetic embryonic enhancers active in the heart, limb, and CNS. Great collab with @alex-stark.bsky.social lab! @ucibiosci.bsky.social @impvienna.bsky.social

Here is a copy of last year's Twitter thread explaining our preprint - jump to (21) for the new stuff 👀

Synergy between cis-regulatory elements can render cohesin dispensable for distal enhancer function

now revised and journal accepted at www.science.org/doi/10.1126/...

🧵👇

Honored to lead off such an amazing set of speakers 🧬 🌟

Enhancer adoption by an LTR retrotransposon generates viral-like particles, causing developmental limb phenotypes - Nature Genetics Activation of an LTR retrotransposon inserted upstream of the Fgf8 gene produces viral-like particles in the mouse developing limb, triggering apoptosis and causing limb malformation. This phenotype c...

Finally out! 🥳 Our paper showing how a transposable element (TE) insertion can cause developmental phenotypes is now published @natgenet.nature.com 🧬🦠🐁
Below is a brief description of the major findings. Check the full version of the paper for more details: www.nature.com/articles/s41588-025-02248-5

Speaking of T-Rex

I think the new highest honor in science is an adorable cartoon of your work 🌟

A dream come true: my first first-author publication! 🧬 🎉 Working to unravel the mysteries of long-range gene regulation has been an incredible journey. Endless gratitude to Evgeny, the lab, and all of the amazing collaborators who helped make this happen 🙌

How do non-coding variants in enhancers lead to disease? Happy to share our recent work, led by @ewholling.bsky.social, in which we discovered that poised chromatin sensitizes enhancers to aberrant activation by non-coding mutations, contributing to disease. www.biorxiv.org/content/10.1... 1/

Modelling and design of transcriptional enhancers - Nature Reviews Bioengineering Enhancers are genomic elements critical for regulating gene expression. In this Review, the authors discuss how sequence-to-function models can be used to unravel the rules underlying enhancer activit...

Awesome summary of the field. An important point is to separate the design method from the oracle model being used. Sometimes, people say they're proposing a new design method but mean a cool new oracle model.

Modelling and design of transcriptional enhancers

www.nature.com/articles/s44...

Genetic factors mediating long-range enhancer-promoter communication in mammalian development - PubMed Enhancers are remotely located noncoding DNA sequences that regulate gene expression in response to developmental, homeostatic, and environmental cues. Canonical short-range enhancers located <50 kb f...

pubmed.ncbi.nlm.nih.gov/39579740/ I liked this thoughtful review

Deletion of a single CTCF motif at the boundary of a chromatin domain with three FGF genes disrupts gene expression and embryonic development Chromatin domains delimited by CTCF can restrict the range of enhancer action. However, disruption of some domain boundaries results in mild gene dysr…

Here is the peer-reviewed version of our study showing how some TAD borders are essential for gene regulation and development.

Loss of a single CTCF motif is sufficient to cause embryonic lethality.

www.sciencedirect.com/science/arti...

We highlighted new research from the past two years on examples of long-range gene regulation - within large TADs, across TADs, and across chromosomes - comparing mechanisms in flies and mammals 🪰❤️🐁.

www.sciencedirect.com/science/arti...

It was exciting to dig into all the new discoveries in long range gene regulation while writing this!

Schematic overview of the proposed mode of action of the newly discovered REX element. Top: An enhancer can activate a gene at a short distance, but not at at long range. Middle: Presence of (C/T)AATTA motifs within an enhancer enable it to act over long distances. Bottom: Coupling a short-range enhancer to the REX element containing the same motifs turns it into a long-range enhancer.

REX - a mammalian "range extender" element that can turn short-distance enhancers into long-distance enhancers.

New preprint from a collaboration led by Grace Bower and Evgeny Kvon.

doi.org/10.1101/2024...