Extended Data Fig. 1: Transcriptional regulatory landscape across tissues and cell types in cattle.

(a) The connection specific index (CSI) matrix consisting of 156 regulons is divided into 6 modules (left). UMAPs illustrate the average AUCell score distribution in different regulon modules (in different colors). Wordcloud plots highlight the top 10 cell lineages and tissues exhibiting the highest average regulatory activity for each submodule, where color intensity and font size reflect the regulatory activity levels. Representative TFs and their corresponding binding motifs are also displayed (right). (b) Zoomed-in view of module 5 (including 23 regulons) identifies sub-module structures and their average regulatory activity in different cell types. (c) Bar plot shows the number of TFs regulating each cell lineage. The x-axis indicates TF counts, color-coded by category: cell-type specific TFs (active in a single cell type), lineage-specific TFs (active across multiple cell types within the same lineage), multi-lineage TFs (active across multiple lineages), and broadly active TFs (tau ≤ 0.85). (d) The TF regulatory network containing 123 highly specific TFs (tau > 0.85) exhibits tissue-specific, cell-type-specific, single-lineage-specific, and multi-lineage-regulated TFs. (e) Heatmap illustrates regulatory activity differences of 682 TFs between males and females. The color gradient indicates the difference in average regulon activity, highlighting a portion of the 45 regulons with an absolute difference greater than 0.15. To ensure unbiasedness, we retained 61 cell types with counts exceeding 50 in both males and females across 19 tissues, where at least one sex exhibited regulatory activity ( > 25% of cells showing regulatory activity).