| 背景 | In vivo, the nucleosome is the basic structural unit of chromatin. It is comprised of about 146 bp of DNA wrapped around a core of eight histones of four different types: H2A, H2B, H3 and H4. Histones are subject to post-translational modifications, such as methylation, acetylation, phosphorylation, mono-ubiquitination, etc. Histone modifications influence multiple chromatin templated processes such as gene transcription, DNA repair and recombination. Besides the “major“ histones, there are some histone variants in specific regions of chromatin or in specific cell types. Histone variants are involved in multiple biological processes including chromosome segregation, DNA repair, transcriptional regulation and mRNA processing.
H2A.Z (also known as H2AFZ, Histone Family Member Z) is a histone H2A family member. It is highly conserved from yeast to human, with 90% of its primary sequence preserved among different species, showing only 60% homology with canonical histone H2A. H2A.Z is found in approximately 10% of mammalian nucleosomes. H2A.Z has been one of the most studied H2A variants in recent years. It plays an important role in different biological processes such as DNA replication, DNA repair, transcription regulation, cell cycle, spermatogenesis, chromosome segregation, centromere structure and maintenance of heterochromatic/euchromatic status. However, different studies reported diverse conclusions in the nucleosome stability and transcriptional regulation. The contradictory roles of H2A.Z in vivo might be explained by different combinations of H2A.Z with other epigenetic regulators, PTMs on H2A.Z and interaction with chromatin binding proteins.
Nucleosomes are more physiologically relevant substrates than histones and histone-derived peptides for in vitro studies. More importantly, some histone methyltransferases are significantly more active, as well as specific, when using nucleosomal substrates in HMT assays, such as DOT1L and NSD family enzymes. Nucleosomes are also widely used in histone methyltransferase screening assays to identify small molecular inhibitors for drug discovery. |
