Characterizing the regulatory logic of transcriptionalcontrol at the DNA sequence level by ensembles ofthermodynamic models

Sabino, A. U.; Guerreiro, D. d. M.; Kim, A.-R.; Ramos, A. F.; Reinitz, J.

doi:10.1101/2025.02.26.640137

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bioRxiv · 10.1101/2025.02.26.640137

Characterizing the regulatory logic of transcriptionalcontrol at the DNA sequence level by ensembles ofthermodynamic models

Sabino, A. U.·Guerreiro, D. d. M.·Kim, A.-R.·Ramos, A. F.·Reinitz, J.

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Abstract

Understanding how the genome encodes the regulatory logics of transcription is a main challenge of the post-genomic era to be overcome with the aid of customized computational tools. We report an automatic framework for analyzing an ensemble of fittings to data of a thermodynamics-based sequence-level model for transcriptional regulation. The fittings are clustered accordingly with their intrinsic regulatory logics. A multiscale analysis enables visualization of quantitative features resulting from the deconvolution of the regulatory profile provided by multiple transcription factors interacting with the locus of a gene. Quantitative experimental data on reporters driven by the whole locus of the even-skipped gene in blastoderm of Drosophila embryos was used for validating our approach. A few clusters of highly active DNA binding sites within the enhancers collectively modulate even-skipped gene transcription. Analysis of variable enhancers length shows the importance of bound protein-protein interactions for transcriptional regulation.

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Sabino, A. U., Guerreiro, D. d. M., Kim, A.-R., Ramos, A. F., Reinitz, J.. 2025-03-01. Characterizing the regulatory logic of transcriptionalcontrol at the DNA sequence level by ensembles ofthermodynamic models. https://doi.org/10.1101/2025.02.26.640137

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