The histones are highly conserved proteins which play an essential role in transcriptional regulation. They form the central octameric core of the nucleosome, acting as a spool for chromatin DNA. Antibody studies have shown histones undergo modification in a number of ways to affect gene expression. We at Novus Biologicals have a wide range of modified histone antibodies in our antibody catalog.
Modification of the chromatin structure activates or represses gene transcription and also plays a role in DNA replication and repair. Remodeling takes place following covalent modification of the N-terminals of the histone tails. Histone antibody research has revealed a large number of modification pathways. They include acetylation, deacetylation, phosphorylation, methylation, ubiquitylation, sumoylation and ADP-ribosylation.
Transcriptional activation is known to be dependent on acetylation of lysine residues within the N-terminal domains. The chromatin is then reconfigured into a more open structure, so it can be accessed by the relevant complexes. Antibody research has suggested L9 acetylation is important to chromatin assembly and histone deposition.
It is thought that transcriptional repression is dependent on lysine deacetylation. It is known that acetylation and methylation can take place on the same on the same lysine residues, allowing both dynamic and more stable modifications, dependant on the stimulus. Lysine methylation is thought to provide a ‘‘memory mark” for active and repressed chromatin.
Lysine is the substrate for a number of posttranslational modifiers, including ubiquitin and SUMO. Using antibodies, researchers have found sumoylation stimulates activity of heat shock factor proteins and the tumour suppressor p53. However, it is mainly associated with repression of transcription factors such as Elk1, c-Myb and c-Jun, and thus their target genes. SUMO is a modifier for both H3 and H4.
Antibody studies focussing on the nucleosomal response have shown stress or mitogenic stimulation results in intense acetylation of H3, followed by phosphorylation at the Ser10 site. Ser10 phosphorylation is associated with mitotic and meiotic chromosome condensation, and with the expression of immediate-early (i.e. rapid response) genes such as c-Myc, c-Jun and c-Fos. Our antibody catalog contains antibodies to these, and many other proteins related to histone modification.