Now published in Current Opinion in Genetics & Development as part of the special issue on Genome Architecture and Expression. 🧬
Part 1: doi.org/10.1016/j.gd...
Part 2: doi.org/10.1016/j.gd...
🔥New work from the Crocker group @justinmcrocker.bsky.social @embl.org on the mechanistic and evolutionary basis of dominance from cis-regulatory variation in Drosophila Congratulations to Noa @ottilie.bsky.social and all the authors 🥳
Come listen to my talk about how enhancers evolve and how promoters emerge from randomly synthesized DNA sequences!
ICYMI: New online! Pleiotropic effects of cis-regulatory mutations
New Preprint! When one enhancer allele changes another's regulatory output, is that bad? We found it could be a feature — interallelic cis-regulatory dominance buffers outputs AND enables evolutionary innovation. Two for one!
Led by @ottilie.bsky.social from @embl.org
doi: doi.org/10.64898/202...
EMBL DB unit
Nature Reviews Genetics
Timothy Fuqua 🏳️🌈
🧬✨ New 2-part review on the evolution of regulatory DNA (enhancers & promoters)! What started as conversations between Gasper Tkačik @istaresearch.bsky.social and our group @embl.org grew into a broader synthesis.
Preprints here:
Part 1: arxiv.org/abs/2601.19681
Part 2: arxiv.org/abs/2601.21480
Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that bind transcription factor (TF) proteins to up- or down-regulate target genes. Decades-long efforts yielded TF-DNA interac...
Our next speaker will be Timothy Fuqua @timothyfuqua.bsky.social with "The Evolution and Emergence of Regulatory DNA", 14th April, 5PM CET.
Sign-up here:
tinyurl.com/prose-seminar2
Nature Reviews Genetics, Published online: 28 May 2026; doi:10.1038/s41576-026-00981-zIn this Comment, Patricia Wittkopp revisits assumptions that cis-regulatory mutations are weakly pleiotropic, ultimately calling for more data to assess the extent to which they are less pleiotropic and deleterious than trans-regulatory mutations.
Dominance is a central principle of genetics, yet the mechanistic basis and the evolutionary consequences of dominance arising from cis-regulatory variation remain poorly understood. We examined the evolutionary trajectories of a pleiotropic developmental enhancer in Drosophila . A genotype–phenotype map between D. melanogaster and D. simulans enhancer sequences reveals extensive epistasis, and many homozygous evolutionary paths reduce transcriptional output. In heterozygotes, however, regulatory dominance masks variants that reduce gene expression, potentially relaxing evolutionary constraints. Using allele-specific reporters and imaging, we show that this dominance arises from interallelic interactions (also known as transvection) reinforced by transcriptional hubs. Importantly, this enhancer dominance is cell-type specific, raising the possibility that it conceals deleterious effects in essential tissues while revealing novel, ectopic activity in others. Interallelic regulatory hubs may therefore expand the range of mutational paths available to diploid genomes while preserving essential transcriptional output. ### Competing Interest Statement The authors have declared no competing interest.
Excited to share my first preprint from my PhD w/ @justinmcrocker.bsky.social. We show that cell type-specific regulatory dominance promotes robustness and evolutionary innovation through interallelic transcriptional hubs, potentially expanding the mutational paths available to diploids. (1/18)
Noa Ottilie Borst
Interallelic cis-regulatory dominance promotes robustness and evolutionary innovation https://www.biorxiv.org/content/10.64898/2026.03.17.712157v1
