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While large genomics datasets have annotated common cis-element features, interpreting and predicting specific environmental responses at the chromatin level are critical ongoing challenges. We combined signal-induced chromatin accessibility changes with transcriptomics and a comprehensive catalogue of chromatin occupancy features for predicting functional signaling responses. Using the Kit receptor tyrosine kinase pathway\u2014a central pro-survival, pro-proliferation, and pro-differentiation pathway in hematopoiesis, erythropoiesis, and other tissues\u2014we mapped the sequence and chromatin features at thousands of Kit signal-responsive cis-elements in the human genome. A subset of Kit-induced changes to chromatin occupancy required upregulation of early growth response-1 (EGR1), uncovering distinct EGR1-sensitive and EGR1-insensitive branches of Kit signaling. Predictions of chromatin features associated with signal responses were tested using CRISPR-mediated\u00a0cis-element disruption, which impaired target gene activation even at very long ranges. These findings define subsets of Kit signaling-dependent cis-regulatory logic which can be applied to interpret how growth factor pathways and cell-type specific transcription factors communicate on chromatin to direct cell behaviors in normal and disease contexts.<\/jats:p>","DOI":"10.1093\/nar\/gkag505","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T11:40:48Z","timestamp":1778326848000},"source":"Crossref","is-referenced-by-count":0,"title":["Predictive modeling of signal-responsive\n                    <i>cis<\/i>\n                    -elements in human red blood cell precursors"],"prefix":"10.1093","volume":"54","author":[{"given":"Venkatasai Rahul","family":"Dogiparthi","sequence":"first","affiliation":[{"name":"Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, 985805 Nebraska Medical Center , Omaha, NE 68124 ,","place":["United 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