To investigate the regulatory PF-03814735 activities of known factors, we conducted a preliminary study using our previous method and ChIP-seq data for 10 major hematopoietic regulators ; however, we were unable to obtain any significant results. This failure prompted us to extend our approach in the following manner. To approximate TFBS activities, we employed cis- and trans-regulatory information from TRANSFAC. Furthermore, to consider the combinatorial regulation of TFs, we incorporated the probabilities of the conditional TF�CTF interactions inferred by LLM. Thus, our approach systematically inferred the regulatory activities of TFBSs, and suggested potential synergistic TF modules. Consequently, we found that motif similarity, the positional distribution of motifs, and expression changes in TFs were the most informative features for the promoter modeling of DEGs. Using LLM, we quantified the TFBS activities on the basis of the fine-tuned explanations of DEGs. Many hematopoietic TFs were included among the transcriptional steady-state gene set, the low-level expression gene set, or the genes expressed at undetectable levels. Throughout this study, we found that the regulatory effects of these TFs and their target sites are essential to explain the regulation of DEGs. This may explain, in part, the observation that our preliminary model using 10 major hematopoietic TFs was not well fitted. We further supported this finding by performing a transplantation assay of LT-HSCs cultured with activated Pparg. Furthermore, we found that these TFs modulated differentially expressed TFs that are Auranofin likely to be important during commitment to specific lineages. However, LLM inferred low probabilities for interactions between known co-operative TF pairs, e.g., Gata2 and Erg and Gata2 and Tal1, which suggests that their co-operation regulates specific gene sets. We identified 142 TFBSs that contributed significantly to the regression models. Among these, 71 TFBSs and 58 TFBSs exhibited a considerable gain or loss of their activities during cell differentiation.