Histone Modifications

The function of histones goes far beyond packaging DNA into the nucleus. Histones are small proteins that are basic due to their high content of arginine and lysine. They were first identified at the end of the 19^th century by the German physiologist Albrecht Kossel¹. The combination of two copies of each of the four core histones H2A, H2B, H3, and H4 together with the DNA wound around them form what is known as the nucleosome core particle. Through the assembly of two histone H3/H4 dimers, a stable tetramer is initially formed^2,3. Two single histone H2A/H2B dimers⁴ finally create the histone octamer.

Figure: Comprehensive map of post-translational modifications of histones H2A, H2B, H3, and H4. A full, high-resolution version of this map is available for download.

The first descriptions of post-translationally modified histones were made as early as the mid-1960s. Methylated lysines were detected in the analysis of histones from calf thymus and a short time later, acetylated lysines could also be identified^5,6. Since then, other modifications such as arginine methylation, phosphorylation, citrullination, biotinylation, ubiquitination, malonylation, and SUMOylation have been associated with histones (Reviewed in 7). Covalent modifications of specific amino acids of histones form the histone code⁸, which is the basis for establishing temporally and spatially differentiated chromatin domains (See the figure above for examples).

The best-known modification of terminal histone regions is the methylation of lysine 9 at histone H3 (H3K9). In mammals, for example, it marks facultative or constitutive heterochromatin, i.e. areas of temporal or permanent gene silencing^9,10. Histone modifications such as H3K9 methylation are the basis of epigenetics because similar to DNA methylation, the regulation of gene expression is passed on independently of the DNA sequence. Further research into the function of histone modifications will therefore advance our understanding of epigenetics. In addition, altered histone modifications have been implicated in the pathogenesis of an increasing number of diseases, including cancer (Reviewed in 11). Rockland's antibody-based tools are being used by scientists around the world in the pursuit of discovering therapeutic options.

Histone Antibodies By Target

Pan-Specific

Histone H3

Histone H4

Histone H2A

References

1. Kossel, A., Über einen peptoartigen Bestandteil des Zellkern. Z. Physiol. Chem. 1884, 8, 511–515.
2. Kornberg, R. D., & Thomas, J. O. (1974). Chromatin structure; oligomers of the histones. Science (New York, N.Y.), 184(4139), 865–868.
3. Roark, D. E., Geoghegan, T. E., & Keller, G. H. (1974). A two-subunit histone complex from calf thymus. Biochemical and biophysical research communications, 59(2), 542–547.
4. Kelley R. I. (1973). Isolation of a histone IIb1-IIb2 complex. Biochemical and biophysical research communications, 54(4), 1588–1594.
5. ALLFREY, V. G., FAULKNER, R., & MIRSKY, A. E. (1964). ACETYLATION AND METHYLATION OF HISTONES AND THEIR POSSIBLE ROLE IN THE REGULATION OF RNA SYNTHESIS. Proceedings of the National Academy of Sciences of the United States of America, 51(5), 786–794.
6. MURRAY K. (1964). THE OCCURRENCE OF EPSILON-N-METHYL LYSINE IN HISTONES. Biochemistry, 3, 10–15.
7. Zhao Y, Garcia BA. Comprehensive Catalog of Currently Documented Histone Modifications. Cold Spring Harb Perspect Biol. 2015;7(9):a025064.
8. Strahl, B. D., & Allis, C. D. (2000). The language of covalent histone modifications. Nature, 403(6765), 41–45.
9. Rice, J. C., Briggs, S. D., Ueberheide, B., Barber, C. M., Shabanowitz, J., Hunt, D. F., Shinkai, Y., & Allis, C. D. (2003). Histone methyltransferases direct different degrees of methylation to define distinct chromatin domains. Molecular cell, 12(6), 1591–1598.
10. Wu, R., Terry, A. V., Singh, P. B., & Gilbert, D. M. (2005). Differential subnuclear localization and replication timing of histone H3 lysine 9 methylation states. Molecular biology of the cell, 16(6), 2872–2881.
11. Audia JE, Campbell RM. Histone Modifications and Cancer. Cold Spring Harb Perspect Biol. 2016;8(4):a019521.