Irregular folding of nucleosomes in the cell: Comment on “Cracking the chromatin code: Precise rule of nucleosome positioning” by Edward N. Trifonov

Abstract

The human body consists of 60 trillion cells, each of which has a total of 2 meters of DNA in the nucleus with a diameter of approximately 10 μm. DNA carries a negatively charged phosphate backbone that produces electrostatic repulsion between adjacent DNA molecules, making it difficult for DNA to coordinate its own folding [1,2]. For the primary level of folding, a negatively charged DNA molecule is wrapped around the basic core, a histone octamer, which consists of the two sets of histones, H2A, H2B, H3, and H4 proteins, and forms a nucleosome structure [3]. Within the nucleosome fibers, where each nucleosome is connected by linker DNA like “beads on a string” [4], how can the histone octamer “see” DNA sequences? Trifonov have provided a thought-provoking review describing the nucleosome positioning signal present on DNA sequences [5]. Surprisingly, three different approaches revealed the same unique sequence motif (CGRAAATTTYCG)n, or (YRRRRRYYYYYR)n in binary form [5]. Since genome functions such as DNA replication, recombination, repair and gene transcription are all dependent upon accessibility to DNA, the nucleosome positioning would represent the “chromatin code”. Therefore, the physico-chemical features of the nucleosome positioning can be analyzed to reveal information regarding the regulation of genome functions. Several interesting questions surrounding nucleosome positioning have emerged from the review [5]: for example, is the identified sequence motif or the 10–11 base pair periodicity conserved in prokaryotes that do not have nucleosomes? Why are the histone proteins in eukaryotes highly conserved whereas genome sequences and the positioning sequence motif are quite divergent among organisms? Which classes of proteins can recognize the positioning motif, the histone octamer itself, histone chaperones, and/or remodeling proteins? Can the epigenetic mark, histone modifications, affect the nucleosome positioning?