Diversity of H2A Histones and Their Effect on Nucleosome Structural Properties

Abstract—

Histone proteins that play an important role in the chromatin dynamics and regulation of gene activity are a key epigenetic factor. They are divided into two broad classes: canonical histones and their variants. The canonical histones are expressed mainly during the S phase of the cell cycle, since they are involved in DNA packaging in the process of cell division. The histone variants are histone genes that are expressed and regulate the chromatin dynamics during the entire cell cycle. Due to the functional and species diversity, different families of variant histones are distinguished. Some proteins are characterized by minor differences from the canonical histones, while others, on the contrary, can have many important structural and functional peculiarities affecting the nucleosome stability and chromatin dynamics. In order to estimate the variability of histones of the H2A family and their effect on the nucleosome structure, we carried out a bioinformatics analysis of amino acid sequences of the H2A family histones. Clustering conducted using a UPGMA method allowed to distinguish two main subfamilies of H2A proteins: short H2A and other H2A variants that demonstrate higher conservatism of amino acid sequences. We also constructed and analyzed multiple alignments for different H2A histone subfamilies. It is important to note that the proteins of short H2A subfamily are not only the least conservative within their family, but also have the peculiarities that have a significant effect on the nucleosome structural properties. In addition, we conducted a phylogenetic analysis of short H2A histones, as a result of which the subfamilies corresponding to the H2A.B, H2A.P, H2A.Q, H2A.L variants were characterized in more detail.