What Are Histones?

Histone is a basic protein in eukaryotic cell chromatin and prokaryotic cells, which together with DNA form the nucleosome structure. They are the main protein components of chromatin, as spools of DNA winding, and play a role in gene regulation, but histones of prokaryotic cells have very weak effects on gene regulation. Without histones, the untwisted DNA in the chromosome would be very long (length-to-width ratio in human DNA exceeds 10 million to 1). For example, each human diploid cell (containing 23 pairs of chromosomes) has about 1.8 meters of DNA, but wrapped around a tissue protein it has about 90 micrometers (0.09 millimeters) of chromatin, which replicates and concentrates during mitosis It results in a chromosome of approximately 120 microns.

Histone means all

In 1884, Albrecht Kosser first discovered histones. It wasn't until the early 1990s that histones were more recognized, not pure inert fillings of the nucleus. This is partly based on the model of Mark Ptashne and others, who believe that transcription is driven by protein-DNA and protein- Protein interactions are largely activated by naked DNA templates, just like bacteria. Later, its regulatory function was discovered.

In the 1980s, Yahli Lorch and Roger Kornberg showed that nucleosomes on core promoters prevented transcription initiation in vitro, and Michael Grunstein demonstrated that histones inhibit transcription in vivo , Resulting in nucleosomes as general gene repressors. ^[1]

Histone is present in

Histone prediction

The latest results show that the overall pattern of histone modification can predict the risk of recurrence of low-grade prostate cancer. The study s first author, Siavash K. Kurdistani, of the University of California, said: This modification mode can eventually be used as a prognosis or diagnostic indicator for prostate or other types of cancer, and it can also be used to predict which patients and patients will deacetylate a class o histone. An indicator of the response of new enzyme inhibitors. Kurdistani explained that certain histone modification patterns can affect gene expression at a certain level, but the exact mechanism is unclear.

Histone regulation

Histone modification and gene expression regulation have been widely demonstrated. Studies by Pierre Etchegary, StevenReppertandcoworkers show that histone modification, especially histone acetylation, is very important for the regulation of mammalian circadian clocks. ^[3]

Clock and Bmal1, key proteins that regulate the circadian clock, drive the expression of three period genes (Per1, 2, 3) and two cytochrome genes (Cry1, 2). The transcripts of these five genes cover the organism for 24 hours. What is strange is that the binding of Clock / Bmal1 to the Per promoter is relatively stable, while their strongest binding to the Cry1 promoter reflects the weakest expression of Cry1. In this article, E discovered that modification of the chromosomal structure determines the transcription of Per and Cry genes.

Researchers have found that the acetylation of histone 3 on the Per1 and Per2 promoters is present throughout the day, and that RNA polymerase II has been recruited to these promoters. When H3 is most strongly bound to RNA polymerase II, Per transcript levels are highest, which suggests that H3 acetylation may promote gene transcription by promoting the recruitment of RNA polymerase II to the promoter. The expression of the Cry locus has a similar correlation.

Researchers have found that p300, which has protein acetylation activity, can complex with Clock in mouse liver cells. Researchers believe that p300 / Bmal1 / Clock binds to the promoter during the day and promotes H3 acetylation. RNA polymerase II is recruited to the promoter and the Per gene is transcribed. At night p300 dissociates from Bmal1 / Clock, causing deacetylation of histones and suppressing gene transcription.

So what is causing the p300 gene's circadian rhythm?

The researchers found that it was the result of Cry's negative regulation of it. The researchers found that Cry1, 2 inhibited p300 / Bmal1 / Clock-driven gene transcription. They think that it may be that Cry destabilizes the p300 / Bmal1 / Clock complex and inhibits its function. The regulation of acetylation on gene expression has been widely known, and this new study has also made it possible to determine that histone acetylation has a wide range of effects on the regulation of gene expression.