{"doi":"10.1016/j.coisb.2020.08.002","title":"Seven myths of how transcription factors read the cis-regulatory code","abstract":"Genomics data are now being generated at large quantities, of exquisite high resolution and from single cells. They offer a unique opportunity to develop powerful machine learning algorithms, including neural networks, to uncover the rules of the cis-regulatory code. However, current modeling assumptions are often not based on state-of-the-art knowledge of the cis-regulatory code from transcription, developmental genetics, imaging and structural studies. Here I aim to fill this gap by giving a brief historical overview of the field, describing common misconceptions and providing knowledge that might help to guide computational approaches. I will describe the principles and mechanisms involved in the combinatorial requirement of transcription factor binding motifs for enhancer activity, including the role of chromatin accessibility, repressors and low-affinity motifs in the cis-regulatory code. Deciphering the cis-regulatory code would unlock an enormous amount of regulatory information in the genome and would allow us to locate cis-regulatory genetic variants involved in development and disease.","journal":"Current Opinion in Systems Biology","year":2020,"id":53120,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":122,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":23592,"name":"Julia Zeitlinger","orcid":"0000-0002-5172-3335","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-18T20:44:25.349797Z","pmid":"33134611","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}