(8/8) Kudos to the Codebook and GRECO-BIT consortium members including @bartdeplancke.bsky.social, @arttujolma.bsky.social, @timhughesto.bsky.social, @halfacrocodile.bsky.social & @alef125.bsky.social, and please see ibis.autosome.org/docs/about_us for the full team.

(7/8) Our in vivo collection, along with other sources as a part of an international effort called the Codebook Project (described in doi.org/10.1101/2024...) revealed many potential new drivers and governors of the genomic “dark matter”.

(6/8) Existing literature suggests that many Dark TFs interact with co-repressors and regulate important biological processes ranging from development and differentiation to immune responses. They also often interact physically with each other.

(5/8) We also released high-confidence binding sites for 137 TFs called triple-overlap sites or “TOP”s, as the intersection of our assays, ChIP-seq, GHT-SELEX, and PWM scans, along with “CTOP”s, a subset of TOPs that are evolutionary conserved.

(4/8) The binding of Dark TFs to repeats and heterochromatin is not due to indirect binding in vivo, rather defined by their intrinsic sequence specificity (as measured by our new in vitro assay, GHT-SELEX doi.org/10.1101/2024...).

(3/8) We detected multiple TFs (particularly Dark TFs) responsible for recognizing specific families of transposable elements, encompassing all major classes (LINEs, SINEs, LTRs, and DNA transposons) and repeat ages.

(2/8) We discovered that roughly half of these TFs bind to unique sites in closed chromatin, enriched for transposable elements, and often without evolutionary conservation; a few characteristics that are the signatures of what we call “Dark TFs”.