Bundle sheath (BS) cells exhibit dramatically structural differences and functional variations at physiological, biochemical and epigenetic levels as compared to mesophyll (M) cells in maize. The regulatory mechanisms controlling functional divergences between M and BS have been extensively investigated. However, BS cell-related regulatory networks are still not completely characterized. To address this, we herein conducted WGCNA-related co-expression assays using bulk M and BS cell RNA-seq data sets and identified a module containing 384 genes highly expressed in BS cells (including 20 hub TFs) instead of M cells. According to the hub TF centered regulatory network, we found that Dof22 and Dof30 might act as key regulators in the regulation of expression of BS-specific genes, and several MYB TFs exhibited a high collaboration with Dof TFs. By comparing the enrichment levels of histone modifications, we found that genes in the aforementioned module were more enriched with histone acetylation as compared to other BS-enriched DEGs with similar expression levels. Moreover, we found that a subset of genes functioning in photosynthesis, protein auto processing and enzymatic activities were significantly enriched with broad H3K4me3. Thus, our study provides evidence showing that regulatory network and histone modifications may play vital roles in the regulation of a subset of genes with important functions in BS cells.