1. Histone methylation

2. Histone phosphorylation

3. Histone Acetylation

4. Histone ubiquitylation

5. Others

2. Histone phosphorylation

Histone phosphorylation has been implicated in numerous processes such as transcription, DNA repair, cell cycle progression and apoptosis, and chromosome condensation. The best-known function of histone phosphorylation takes place during cellular response to DNA damage, when phosphorylated histone H2A(X) demarcates large chromatin domains around the site of DNA breakage ^[2].

Histone phosphorylation can occur on serine, threonine and tyrosine residues and constitutes an essential part of the "histone code," or combinatory function of PTMs on chromatin. Phosphorylation of histones can also be an important regulatory signal. Histone H3 phosphorylation is known to play important roles in both transcription and chromosome condensation during mitosis. Histone H2B phosphorylation condenses the chromatin and is involved in apoptosis. Phosphorylation of H2A and H4 occur, but the downstream effects of phosphorylation of these subunits are unknown ^{[3] [4]}.

Here, we list part of CUSABIO phosphorylated histone antibodies on the table 2.

Table 2. The List of CUSABIO phosphorylated Histone Antibodies

3. Histone Acetylation

Histone acetylation is triggered by the enzymatic addition of an acetyl group (COCH3) from acetyl coenzyme A. The process of histone acetylation is closely involved in the regulation of many cellular processes, including chromatin dynamics and transcription, gene silencing, cell cycle progression, apoptosis, differentiation, DNA replication, DNA repair, nuclear import, and neuronal repression. But the most common function of histone acetylation is associated with an open chromatin structure. This makes chromatin accessible to transcription factors and can significantly increase gene expression.

Histone acetylation is largely targeted to promoter regions. For example, acetylation of histone H3 and histone H4 is involved in the regulation of chromatin structure and the recruitment of transcription factors to gene promoters. Histone acetyltransferases (HAT) and deacetylases (HDACs) are the enzymes responsible for writing and erasing the acetylation of histone tails. Lysine residues within histone H3 and H4 are preferential targets for HAT complexes.

Here, we list part of CUSABIO acetylated histone antibodies on the table 3.

Table 3. The List of CUSABIO acetylated Histone Antibodies

4. Histone ubiquitylation

Histone ubiquitination, one of the histone post-transcriptional modifications, has been discovered for more than three decades. As histones are the most abundant ubiquitinated proteins, their ubiquitination plays critical roles in many processes in the nucleus, involving transcription, maintenance of chromatin structure, and DNA repair.

Monoubiquitination of H2A and H2B have been clearly implicated in transcriptional regulation. H2Aub occupation is more frequently correlated with gene silencing, while H2Bub is mostly associated with transcription activation ^[5]. In addition to transcription regulation, monoubiquitinated H2B is also required for chromatin function via other ways. H2Bub has the role of chromatin boundary integrity, and loss of H2Bub leads to the spreading of other histone modifications ^[6]. H2Bub is also shown to play an important role in homologous recombination through chromatin remodeling by recruiting chromatin remodeling factors. Cells lacking RNF20 or expressing H2B K120R, which lacks ubiquitin conjugation site, exhibit defects in HRR ^[7].

In addition to polyubiquitination, monoubiquitination of histones H2A, H2B, and H2AX also occurs at the sites of DNA damage.

5. Others

Besides the histone modifications mentioned earlier, there also have several other histone modifications, such as sumoylation and Biotinylation. Histone sumoylation, as an example, is a post-translational modification directed by an enzymatic cascade in which Small Ubiquitin-like Modifier (SUMO) proteins are attached to or detached from other proteins to change their function in cells. Detection of SUMO conjugation or protein sumoylation can help researchers understand how this modification plays a role in regulating nuclear protein activity and in certain cellular processes, such as transcriptional regulation, apoptosis, nuclear-cytosolic transport, response to stress, protein stability, and progression through the cell cycle.

References

[1] Greer, E. L. & Shi, Y. Histone methylation: a dynamic mark in health, disease and inheritance [J]. Nat. Rev. Genet. 2012, 13, 343–57.

[2] Ye Zhang, Karen Griffin, et al. Phosphorylation of Histone H2A Inhibits Transcription on Chromatin Templates [J]. J Biol Chem. 2004, 279(21):21866-72.

[3] Berger, S. L. Histone modifications in transcriptional regulation [J]. Curr. Opin. Genet. 2002, Dev. 12, 142–148.

[4] Wang L. Cheung, Kozo Ajiro, et al. Apoptotic Phosphorylation of Histone H2B Is Mediated by Mammalian Sterile Twenty Kinase [J]. Cell. 2003, 113, 507–517.

[5] Zhou W., Zhu P., et al. Histone H2A monoubiquitination represses transcription by inhibiting RNA polymerase II transcriptional elongation [J]. 2008, Mol. Cell 29, 69–80.

[6] Ma MK, Heath C, et al. Histone crosstalk directed by H2B ubiquitination is required for chromatin boundary integrity [J]. PLoS Genet. 2011 Jul; 7(7):e1002175.

[7] Nakamura K, Kato A, et al. Regulation of homologous recombination by RNF20-dependent H2B ubiquitination [J]. Mol Cell. 2011, Mar 4; 41(5):515-28.