The basic building blocks of chromatin are referred to as the nucleosome. Nucleosomes play major role in transcriptional regulation, ranging from repression through occlusion of binding sites for transcription factors, to activation through spatial juxtaposition of transcription factor-binding sites. Examining the position of nucleosome in CD80 promoter is essential to detect the mechanism of tissue specific transcriptional regulation at chromatin level. The CD80 is the most potent of all of the co-stimulatory molecule, expressed on the surface of B cells upon antigen stimulation. The expression of CD80 is tightly regulated, normally limited to only a few cell types including B cells. Therefore this study is important, how nucleosomes become positioned during gene regulation in diverse murine tissues and cell lines. The upstream region of CD80 promoter was examined for its nucleosomal organization by low resolution analysis of MNase-southern blot assay. Four nucleosomes were detected in all murine tissues and cells screened for this analysis. Curiously, similar pattern of nucleosome positioning was detected in all the tissues and cell lines screened. This results conclude that there is no regulation at the level of nucleosome positioning in murine CD80 promoter. However, there must be a regulatory mechanism involved in these tissues either at the molecular level or chromatin level or both as the CD80 gene expression was detected in organs rich in antigen presenting cells, spleen, thymus and lung. This was addressed by possible remodeling mechanism through covalent modification of histone proteins which mark for active transcription and repression of gene regulation.