Histone deacetylases (HDACs) control histone acetylation levels by removing acetyl group from lysine residues. Maize (Zea mays) HDAC HDA101 influences several aspects of development, including kernel size; however, the molecular mechanism by which HDA101 affects kernel development remains unknown. In this study, we find HDA101 regulates the expression of transfer cell-specific genes, suggesting their mis-regulation may be associated with defects in differentiation of transfer cells and smaller kernels of hda101 mutants. To investigate HDA101 function during early stages of seed development, we performed genome-wide mapping of HDA101 binding sites. We observed that HDA101 mainly targets highly and intermediately expressed genes. Although loss of HDA101 can induce histone hyper-acetylation of its direct targets, this often does not involve variation in transcription. A small subset of inactive genes that must be negatively regulated during kernel development are also targeted by HDA101 and its loss leads to hyper-acetylation and increased expression of these genes. Finally, we report HDA101 interacts with members of different chromatin remodeling complexes, such as NFC103/MSI1 and SNL1/SIN3-like co-repressors. Taken together, our results reveal a complex genetic network regulated by HDA101 during seed development and provide insights into the different mechanisms of HDA101-mediated regulation of transcriptionally active and inactive genes.