NBP-45, a novel nucleosomal binding protein with a tissue-specific and developmentally regulated expression

Here we characterize a novel murine nuclear protein, which we named NBP-45, that is related to the ubiquitous nuclear proteins HMG-14/-17, binds speci fically to nucleosome core particles, and can function as a transcriptional activator. NBP-45 mRNA is expressed at low levels and in variable amounts in all mouse tissues tested but is especially abundant in RNA extracted fro m 7-day-old mouse embryos, suggesting that it functions in early embryonic development, NBP-45 is composed of 406 amino acids and is encoded by a sing le size transcript. The region spanning the N-terminal 85 amino acids conta ins three segments that are highly homologous to functionally important dom ains in the HMG-14/-17 protein family: the nuclear localization signal, the nucleosome binding domain, and the chromatin unfolding domain. The protein region spanning the C-terminal 321 amino acids has a 42% content of negati vely charged residues. The first 23 amino acids contain a region necessary for nuclear entry of the protein, the region spanning residues 12-40 is the main nucleosomal binding domain of the protein, and the negatively charged , C-terminal domain is necessary for transcription activation. The function al domains of NBP-45 are indicative of a nuclear protein that binds to nucl eosomes, thereby creating a chromatin region of high local negative charge. Our studies establish the nucleosomal binding domain as a protein motif th at is present in other than just the ubiquitous HMG-14/-17 proteins. We sug gest that the nucleosomal binding domain motif is a protein module that fac ilitates binding to nucleosomes in chromatin.