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From ATAC to FOODIE: Transcription Factor Research Enters the Era of Cooperative Decoding

08-22-2026 04:42 AM CET | Business, Economy, Finances, Banking & Insurance

Press release from: ABNewswire

From ATAC to FOODIE: Transcription Factor Research Enters

Nanjing, Jiangsu, China - August 21, 2026 - FOODIE advances transcription factor research beyond chromatin accessibility by resolving TF footprints, occupancy, and cooperative binding at near single-base resolution. Combined with CUT&Tag, it offers complementary insight into TF-chromatin interactions and regulatory mechanisms.

Over the past decade, ATAC-Seq has become a standard tool for profiling chromatin accessibility. By leveraging Tn5 transposome to capture open chromatin regions, ATAC-Seq enables rapid identification of potential regulatory elements. However, chromatin accessibility alone does not directly indicate true transcription factor occupancy, making footprint-level analysis essential for resolving true binding events and cooperativity.

Recently, the research team led by Xiaoliang Sunney Xie published a study in PNAS introducing FOODIE (Footprinting with Deaminase), a novel footprinting approach based on deaminase chemistry. Building on ATAC-Seq, FOODIE integrates a deaminase reaction to enable near single-base-resolution mapping of transcription factor footprints and single-molecule analysis of occupancy and cooperative binding.

FOODIE uses a double-stranded DNA deaminase to convert cytosine (C) into uracil (U). DNA regions not occupied by proteins can be accessed and deaminated by the enzyme, whereas transcription factor-bound regions are protected by steric hindrance. Sequencing-based quantification of C-to-U conversion therefore enables high-resolution mapping of transcription factor footprints and occupancy.

Image: https://vazyme-singapore-website-prod.s3.ap-southeast-1.amazonaws.com/d2027d135fec4f2f8b55f0460b5b7abc

Fig.1 FOODIE workflow: Genome-wide TF binding site mapping made simple[1].

FOODIE sets a new standard with near single-base resolution and single-molecule insight into transcription factor binding. It quantifies locus-specific occupancy as bound/total molecules, distinguishing transient from stable interactions for a more precise measure of regulatory strength.

Image: https://vazyme-singapore-website-prod.s3.ap-southeast-1.amazonaws.com/4a4220cba0524526b14f4cb30d602da3

Fig.2 FOODIE maps TF footprints via single-molecule C-to-U conversion[1].

Furthermore, FOODIE enables precise characterization of transcription factor cooperativity using a quantitative cooperativity parameter ( = ad/bc).

Image: https://vazyme-singapore-website-prod.s3.ap-southeast-1.amazonaws.com/698445b2dbfc47279c48427861dbf353

Fig.3 TFs cooperativity inferred from single-molecule reads[1].

When combined with CUT&Tag, FOODIE and CUT&Tag together can provide complementary layers of information for characterizing transcription factor-chromatin interactions. CUT&Tag identifies genomic enrichment regions, whereas FOODIE captures direct protein-DNA contact footprints. Using CTCF as an example, integration of FOODIE footprints with CUT&Tag peaks enables refined analysis of true occupancy sites and local binding features.

Image: https://vazyme-singapore-website-prod.s3.ap-southeast-1.amazonaws.com/982a0205c8444d5bafbfaf5c50592777

Fig.4 Integrated analysis of FOODIE and CUT&Tag data

Moreover, FOODIE could further resolve the functional division of transcription factors within the same regulatory region. For example, CUT&Tag could reveal the co-localization of CTCF and YY1 at transcription start site (TSS) regions, FOODIE could demonstrate that their actual binding positions differ: CTCF predominantly occupies upstream and boundary regions, while YY1 is enriched near the core transcription start site (TSS), indicating that the integration of CUT&Tag and FOODIE may enable high-resolution characterization of transcription factor occupancy and functional specialization.

Image: https://vazyme-singapore-website-prod.s3.ap-southeast-1.amazonaws.com/1c7a9314749d40c5b7f88734debcb1ad

Fig.5 High-resolution functional partitioning of TFs within regulatory regions.

Overall, FOODIE is not intended to replace existing technologies, but rather to elevate the level of regulatory information that can be obtained. CUT&Tag maps transcription factor binding regions, ATAC-Seq profiles chromatin accessibility, and FOODIE resolves transcription factor footprints and cooperativity at near single-base resolution. When combined with CUT&Tag, FOODIE provides single-base-resolution footprint and cooperativity information, enabling further exploration of regulatory mechanisms beyond binding-site identification. This development provides new perspectives for investigating complex biological processes and disease mechanisms.

Table 1. Comparison of ATAC-Seq, FOODIE, and CUT&Tag methods

Image: https://vazyme-singapore-website-prod.s3.ap-southeast-1.amazonaws.com/e3810883d85540ccbf8bdd074b9d4ae3

[1]He R, Dong W, Wang Z, Xie C, Gao L, Ma W, et al.

Genome-wide single-cell and single-molecule footprinting of transcription factors with deaminase. Proc Natl Acad Sci U S A. 2024;121(52):e2423270121. doi:10.1073/pnas.2423270121

About us

Vazyme (688105.SH) is a global technology and service provider that dedicated to the design, manufacture, and application of bioactive proteins and continuously expands the application fields of core technologies in life science, in vitro diagnostics, bio-medicine, and others. To meet the varying needs of our customers and partners, we have developed over 600 types of genetically engineered recombinant enzymes and over 2,500 types of high-performance materials and over 2,000 end products.

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