Sign in

Jason Tan

@yjtan.bsky.social
41 followers 55 following 13 posts

CS PhD student at Stanford; prev Rice CS

PostsRepliesMedia
Jason Tan @yjtan.bsky.social · 11/08/2026
Good q, short answer yes. Predicted CREs for RNASEH2A and COPZ1 in Fulco 2019 Fig.S2 contact these genes but do not regulate them and instead regulate a diff gene. Though only BAX in the sparse CRISPRi data fits the more visually appealing defn of "skipping" := needing an arc over a gene
000
Reposted by Jason Tan
Abby Thurm @abbythurm.bsky.social · 30/06/2026
Great experience compiling years of collective screening experience to produce what we hope is a comprehensive protocol for others to accessibly scale up experiments! And some fun new data hidden in there :) @joshtycko.com www.nature.com/articles/s41...
nature.com
High-throughput measurements of protein domain functions using magnetic separation - Nature Protocols
This Protocol presents a scalable magnetic separation-based method for screening large protein domain libraries in mammalian cells, providing a simple and quantitative alternative to fluorescence-acti...
094
Jason Tan @yjtan.bsky.social · 30/06/2026
This was all made possible by @judhajeetray.bsky.social, @mayayayas.bsky.social, Ben Doughty and my advisors who supported me down this rabbit hole. We look forward to your feedback! We’re excited explore possible mechanisms of responsiveness and incorporate it into more predictive modeling.
020
Jason Tan @yjtan.bsky.social · 30/06/2026
Editing these motifs modulates promoter responsiveness to produce a non-intuitive effect: basal activity increases but maximum output decreases! Edits also redistribute TSSs, implicating recruitment or assembly of the PIC as possible mechanisms to mediate responsiveness.
160
Jason Tan @yjtan.bsky.social · 30/06/2026
Finally, how is responsiveness encoded? Most promoters lack classical “core promoter motifs” yet vary in responsiveness. By leveraging ProCapNet from Kelly Cochran and @anshulkundaje.bsky.social, we nominate several sequence motifs in the core promoter associated with differential responsiveness.
130
Jason Tan @yjtan.bsky.social · 30/06/2026
Genes with responsive promoters are regulated by more enhancers and sensitive to their perturbation. Genes with non-responsive promoters (many housekeeping genes) are insensitive to and skipped by enhancers.
131
Jason Tan @yjtan.bsky.social · 30/06/2026
Incorporating responsiveness into the Activity-by-Contact model improves prediction of native regulation and explains 2 long-observed phenomena: 1) Why are housekeeping genes often insensitive to distal enhancers? 2) How do enhancers skip active genes?
131
Jason Tan @yjtan.bsky.social · 30/06/2026
We find that promoters differ dramatically in their intrinsic capacity to be activated by *any* enhancer (>100-fold vs 1.1-fold) -- from highly- to effectively non-activatable! Promoter responsiveness scales the magnitude of activation while enhancer rank-order stays similar.
151
Jason Tan @yjtan.bsky.social · 30/06/2026
To cleanly re-assess E-P compatibility, we develop improved assays and apply them across >25,000 E-P pairs, including 7 endogenous loci supported by previous CRISPR tiling experiments.
120
Jason Tan @yjtan.bsky.social · 30/06/2026
Surprisingly, confounders in widely used upstream and STARR-seq designs distort measurements of enhancer activity and lead to contradictory conclusions about E-P compatibility!
120
Jason Tan @yjtan.bsky.social · 30/06/2026
Prior studies used different reporter designs. After some tinkering, we began to suspect two variables were confounding results; so, we compared 6 designs head-to-head. Do the same E-P pairs give different results in different assays?
110
Jason Tan @yjtan.bsky.social · 30/06/2026
Does E-P compatibility play a role? We and others have used massively parallel reporter assays (MPRAs) to test thousands of combinations. Yet, findings have ranged widely — from enhancers activating all promoters equally to highly specific activation of select promoters.
110
Jason Tan @yjtan.bsky.social · 30/06/2026
Enhancer-promoter (E-P) wiring is complex and hard to predict. Decoding the underlying factors is essential for interpreting human genetic variants, modeling gene regulation, and designing gene therapies.
110
Jason Tan @yjtan.bsky.social · 30/06/2026
Does every enhancer work with every promoter? With @jengreitz.bsky.social and Will Greenleaf, we revisit this long-debated question and resolve an outstanding contradiction in the field. A tour 🧵👇 www.biorxiv.org/content/10.6...
biorxiv.org
Intrinsic promoter responsiveness dictates sensitivity to transcriptional activation by enhancers
Enhancers activate specific target promoters, but whether intrinsic enhancer-promoter compatibility contributes to this specificity is debated. Recent studies using different reporter assays have reac...
37239