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Timothy Fuqua 🏳‍🌈

@timothyfuqua.bsky.social

630 followers 820 following 130 posts

Postdoc in Andreas Wagner's lab. I'm currently obsessing over how new promoters and enhancers emerge de novo. Also dogs 🐶 and triathlon 🏊 🚲 🏃. He/him 🏳‍🌈. timothyfuqua.com

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Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · May 22

Happy to announce that our study on the latent cis-regulatory potential of mobile DNA is officially published!

TLDR: mobile DNA in bacteria (Insertion Sequences) have a proclivity for evolving new promoters. At least 25% of them probably already encode functional promoters as well.

The latent cis-regulatory potential of mobile DNA in Escherichia coli - Nature Communications

The mechanism and extent to which transposons can alter the gene expression of their hosts is not well understood. This study finds that in the IS3 family of transposable elements in E.coli, de-novo p...

www.nature.com

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Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · 5d

Congrats!!

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Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · 8d

Editor’s choice 😎 and it‘s a short read 😉.

We show evidence of de novo genes emerging from the Nucleosome Depleted Regions (NDRs) of yeast genomes. They are biased towards encoding transmembrane domains because of the NDRs too!

Journal of Evolutionary Biology @jevbio.bsky.social · 8d

SEPTEMBER's EDITOR's CHOICE:

Intergenic, repetitive motifs that act as nucleosome repleted regions in the budding yeast genome, have evolved de novo into novel protein-coding genes:

doi.org/10.1093/jeb/...

@vakirlis.bsky.social
@timothyfuqua.bsky.social

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Reposted by Timothy Fuqua 🏳‍🌈

Siân Culley @superresolusian.bsky.social · 9d

BioImage analysis friends - King's are recruiting for a full-time, permanent facility position! Come and work with fun microscopes and fun people (and me!) - please share! www.kcl.ac.uk/jobs/126345-...

Bioimage Analysis Specialist | King's College London

www.kcl.ac.uk

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Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · 21d

Transposons turning into enhancers again! #TEsky

A subset of transposable elements as mechano-response enhancer elements in controlling human embryonic stem cell fate - Nature Cell Biology

Sun et al. identify a subset of transposable elements that serve as mechano-response enhancer elements that control gene expression and human stem cell fate.

www.nature.com

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Reposted by Timothy Fuqua 🏳‍🌈

Max-Planck-Gesellschaft @maxplanck.de · 29d

Springboard for an international scientific career! 🧬🧪🔭⚛️🧠🌱 Call for #MaxPlanckResearchGroups launched; applications are possible until October 14, 2025 www.mpg.de/max-planck-r... #ScienceCareer

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Reposted by Timothy Fuqua 🏳‍🌈

Alejandro Montenegro @aemonten.bsky.social · Sep 3

"We propose a model in which TF binding is not determined by individual binding sites, but rather by the sum of multiple, overlapping binding sites."

www.nature.com/articles/s41...

Multiple overlapping binding sites determine transcription factor occupancy - Nature

A new method enables comprehensive screening and identification of low-affinity DNA binding sites for transcription factors, and reveals that nucleotides flanking high-affinity binding sites create ov...

www.nature.com

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Reposted by Timothy Fuqua 🏳‍🌈

Jeffrey Ross-Ibarra @jrossibarra.bsky.social · Sep 1

What's the difference between dominance and epistasis? Two physically distinct mutations in a gene interact such that the het is identical to one of the homozygotes. If I define the gene as a locus, we call this dominance. If I define each bp as a locus, we call this epistasis.

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Reposted by Timothy Fuqua 🏳‍🌈

Anshul Kundaje @anshulkundaje.bsky.social · Aug 28

Here's the preprint if interested

www.biorxiv.org/content/10.1...

Dissecting the cis-regulatory syntax of transcription initiation with deep learning

Despite extensive characterization of mammalian Pol II transcription, the DNA sequence determinants of transcription initiation at a third of human promoters and most enhancers remain poorly understoo...

www.biorxiv.org

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Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 28

That’s very exciting! I look forward to reading that!

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Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 28

But my gut tells me you’re right. The drift barrier probably determines the extent by which promoter emergence differs between genomic and random DNA in different species.

Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 28

Different for sure, but more complex? I.e. what percent of random sequences have eukaryotic promoter activity? A TATA box has a similar amount of info as a -10 box, right?

Selection plays a larger role in prokaryotes. The question =what selective forces removed the promoter-like sequences in proks?

Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 28

Thanks! And fair points. I used the word “simple” to avoid unpacking the term “low information content” in the intro. But now I see that this is also problematic. Promoters, prokaryotic or eukaryotic, are obviously very exciting and mysterious, and far from simple to understand ☺️

Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 28

Yes, exactly! The question of which evolutionary forces have pushed it away from being a promoter, however, are not so clear.

Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 28

Thanks! It's been a wild ride 😅

Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 28

(4/4) …we release codes and data with the BioRxiv submission, and welcome all feedback and criticisms. Let me know if I need to cite your work in the next revision or if a script isn't working!

GitHub - tfuqua95/random-genomic

Contribute to tfuqua95/random-genomic development by creating an account on GitHub.

github.com

Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 28

(3/4) …promoters emerge ~3 times more readily from random DNA than from genomic DNA. Basically this is because genomic sequences are impoverished in proto-sites for regulatory proteins compared to random DNA.

As always…

Two side-by-side boxplots oriented vertically. The vertical y-axis is the probability that a mutation will make a new promoter, ranging from 0 to 0.4. The left boxplot is for genome DNA sequences in pink. The right boxplot is for random DNA sequences in purple. Both distributions have outliers towards 0.4. The purple boxplot is significantly higher than the pink boxplot.

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Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 28

(2/4) …created mutagenesis libraries from 225 genomic sequences and 60 randomly synthesized sequences without promoter activity, and measured their ability to create new promoters using Sort-Seq. We found that…

A schematic image of a described experiment. First, cartoon images of mutagenized DNA sequences originating from genomic (pink) and random (purple) DNA. Second, the DNA is sandwiched between reporter proteins (blue and orange arrows) on a plasmid. Third, cartoon bacteria are colored in different shades and hues of blue and orange to represent new promoters. Fourth: the bacteria are put into different categories based on those shades and hues. Fifth: a list of DNA sequences with promoter "scores" for the reporter proteins.

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Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 28

Excited / nervous to share the “magnum opus” of my postdoc in Andreas Wagner’s lab!

"De-novo promoters emerge more readily from random DNA than from genomic DNA"

This project is the accumulation of 4 years of work, and lays the foundation for my future group. In short, we… (1/4)

De-novo promoters emerge more readily from random DNA than from genomic DNA

Promoters are DNA sequences that help to initiate transcription. Point mutations can create de-novo promoters, which can consequently transcribe inactive genes or create novel transcripts. We know lit...

www.biorxiv.org

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Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 25

Is there any other way to be in a FACS facility? :P Also usually only finding a booking at "9 in the afternoon"

Reposted by Timothy Fuqua 🏳‍🌈

Seirian Sumner @waspwoman.bsky.social · Aug 23

If a wasp visits your picnic this wknd, what’s she after?
#HamOrJam?

Worker wasps hunt protein for the larvae but need sugar themselves.

Help us learn about their food preferences-tell us what wasps want at your picnic.
#CitizenScience
#WaspPicnicSurvey

docs.google.com/forms/d/e/1F...

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Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 20

Fun fact: that exact analysis is why I suggested to @vakirlis.bsky.social that we look for motifs in his iORFs for that paper!

Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 20

I once did a MEME analysis on the sequences with a bias towards creating new promoters. The genomic sequences recapture the known enriched octamers in the E. coil genome and proto-10 boxes. Random sequences proto-10 boxes as well. I’d say having a proto-10 box is my best prediction signature ATM.

Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 20

I’ve looked a bit at AT-content differences, but this doesn’t lead to anything. If you have time, let’s chat! It’s very easy to do these analyses, and I could put them in the paper before submitting it!

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Timothy Fuqua 🏳‍🌈 @timothyfuqua.bsky.social · Aug 20

Thanks! Information theory basically tells us that we can expect X amount of RNA polymerase and TF binding sites by pure chance in random DNA. The genome just has less of these binding sites. So it’s actually the absence of sites in the genome that creates the bias.

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Reposted by Timothy Fuqua 🏳‍🌈

Journal of Molecular Evolution @jmolev.bsky.social · Aug 20

Nice talk from @timothyfuqua.bsky.social on the capacity of bacterial genomes to evolve promoters 'de novo'. One impt number: what % of genomic sequence is, or is mutationally close to, being a promoter? Another, more overlooked: how does this compare to the # in random sequence? #ESEB2025

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