Skip to main content
Log in

Diversity of H2A Histones and Their Effect on Nucleosome Structural Properties

  • RESEARCH ARTICLE
  • Published:
Moscow University Biological Sciences Bulletin Aims and scope Submit manuscript

Abstract

Histone proteins that play an important role in the chromatin dynamics and regulation of gene activity are a key epigenetic factor. They are divided into two broad classes: canonical histones and their variants. The canonical histones are expressed mainly during the S phase of the cell cycle, since they are involved in DNA packaging in the process of cell division. The histone variants are histone genes that are expressed and regulate the chromatin dynamics during the entire cell cycle. Due to the functional and species diversity, different families of variant histones are distinguished. Some proteins are characterized by minor differences from the canonical histones, while others, on the contrary, can have many important structural and functional peculiarities affecting the nucleosome stability and chromatin dynamics. In order to estimate the variability of histones of the H2A family and their effect on the nucleosome structure, we carried out a bioinformatics analysis of amino acid sequences of the H2A family histones. Clustering conducted using a UPGMA method allowed to distinguish two main subfamilies of H2A proteins: short H2A and other H2A variants that demonstrate higher conservatism of amino acid sequences. We also constructed and analyzed multiple alignments for different H2A histone subfamilies. It is important to note that the proteins of short H2A subfamily are not only the least conservative within their family, but also have the peculiarities that have a significant effect on the nucleosome structural properties. In addition, we conducted a phylogenetic analysis of short H2A histones, as a result of which the subfamilies corresponding to the H2A.B, H2A.P, H2A.Q, H2A.L variants were characterized in more detail.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

REFERENCES

  1. Talbert, P.B. and Henikoff, S., Histone variants at a glance, J. Cell Sci., 2021, vol. 134, no. 6, p. jcs244749.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Draizen, E.J., Shaytan, A.K., Mariño-Ramírez, L., Talbert, P.B., Landsman, D., and Panchenko, A.R., HistoneDB 2.0: a histone database with variants—an integrated resource to explore histones and their variants, Database, 2016, vol. 2016, p. baw014.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Malik, H.S. and Henikoff, S., Phylogenomics of the nucleosome, Nat. Struct. Mol. Biol., 2003, vol. 10, no. 11, pp. 882–891.

    Article  CAS  Google Scholar 

  4. Kustatscher, G., Hothorn, M., Pugieux, C., Scheffzek, K., and Ladurner, A.G., Splicing regulates NAD metabolite binding to histone macroH2, Nat. Struct. Mol. Biol., 2005, vol. 12, no. 7, pp. 624–625.

    Article  CAS  PubMed  Google Scholar 

  5. Yelagandula, R., Stroud, H., Holec, S., Zhou, K., Feng, S., Zhong, X., Muthurajan, M., Nie, X., Kawashima, T., Groth, M., Luger, K., Jacobsen, S., and Berger, F., The histone variant H2A.W defines heterochromatin and promotes chromatin condensation in Arabidopsis, Cell, 2014, vol. 158, no. 1, pp. 98–109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tanaka, M., Hennebold, J.D., Macfarlane, J., and Adashi, E.Y., A mammalian oocyte-specific linker histone gene H1oo: homology with the genes for the oocyte-specific cleavage stage histone (cs-H1) of sea urchin and the B4/H1M histone of the frog, Development, 2001, vol. 128, no. 5, pp. 655–664.

    Article  CAS  PubMed  Google Scholar 

  7. Jiang, D., Borg, M., Lorković, Z.J., Montgomery, S.A., Osakabe, A., Yelagandula, R., Axelsson, E., and Berger, F., The evolution and functional divergence of the histone H2B family in plants, PLoS Genet., 2020, vol. 16, no. 7, p. e1008964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Strickland, M., Strickland, W.N., Brandt, W.F., Von Holt, C., and Wittmann-Liebold, B., The complete amino-acid sequence of histone H2B(3) from sperm of the sea urchin Parechinus angulosus, Eur. J. Biochem., 1978, vol. 89, no. 2, pp. 443–452.

    Article  CAS  PubMed  Google Scholar 

  9. Kawashima, T., Lorković, Z.J., Nishihama, R., Ishizaki, K., Axelsson, E., Yelagandula, R., Yelagandula, R., Kohchi, T., and Berger, F., Diversification of histone H2A variants during plant evolution, Trends Plant Sci., 2015, vol. 20, no. 7, pp. 419–425.

    Article  CAS  PubMed  Google Scholar 

  10. Ueda, K., Suzuki, M., Ono, M., Ide, N., Tanaka, I., and Inoue, M., Male gametic cell-specific histone gH2A gene of Lilium longiflorum: Genomic structure and promoter activity in the generative cell, Plant Mol. Biol., 2005, vol. 59, no. 2, pp. 229–238.

    Article  CAS  PubMed  Google Scholar 

  11. Molaro, A., Young, J.M., and Malik, H.S., Evolutionary origins and diversification of testis-specific short histone H2A variants in mammals, Genome Res., 2018, vol. 28, no. 4, pp. 460–473.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Churchill, M.E. and Suzuki, M., “SPKK” motifs prefer to bind to DNA at A/T-rich sites, EMBO J., 1989, vol. 8, no. 13, pp. 4189–4195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zambrano-Mila, M.S., Aldaz-Villao, M.J., and Casas-Mollano, J.A., Canonical histones and their variants in plants: evolution and functions, in Epigenetics in Plants of Agronomic Importance: Fundamentals and Applications, Alvarez-Venegas, R., De-la-Peña, C., Casas-Mollano, J., Eds., Cham: Springer-Verlag, 2019, pp. 185–222.

    Google Scholar 

  14. Larkin, M.A., Blackshields, G., Brown, N.P., Chenna, R., McGettigan, P.A., McWilliam, H., Valentin, F., Wallace, I.M., Wilm, A., Lopez, R., Thompson, J.D., Gibson, T.J., Higgins, D.G., Clustal W and Clustal X version 2.0, Bioinformatics, 2007, vol. 23, no. 21, pp. 2947–2948.

    Article  CAS  PubMed  Google Scholar 

  15. Wheeler, T.J. and Kececioglu, J.D., Multiple alignment by aligning alignments, Bioinformatics, 2007, vol. 23, no. 13, pp. i559– i568.

    Article  CAS  PubMed  Google Scholar 

  16. Edgar, R.C., MUSCLE: multiple sequence alignment with high accuracy and high throughput, Nucleic Acids Res., 2004, vol. 32, no. 5, pp. 1792–1797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Guindon, S., Dufayard, J.F., Lefort, V., Anisimova, M., Hordijk, W., and Gascuel, O., New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0, Syst. Biol., 2010, vol. 59, no. 3, pp. 307–321.

    Article  CAS  PubMed  Google Scholar 

  18. Beitz, E., TEXshade: shading and labeling of multiple sequence alignments using LaTeX2e epsilon, Bioinformatics, 2000, vol. 16, no. 2, pp. 135–139.

    Article  CAS  PubMed  Google Scholar 

  19. Jiang, X., Soboleva, T.A., and Tremethick, D.J., Short histone H2A variants: small in stature but not in function, Cells, 2020, vol. 9, no. 4, p. 867.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chew, G.L., Bleakley, M., Bradley, R.K., Malik, H.S., Henikoff, S., Molaro, A., and Sarthy, J., Short H2A histone variants are expressed in cancer, Nat. Commun., 2021, vol. 12, no. 1, p. 490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Dryhurst, D., Ishibashi, T., Rose, K.L., Eirín-López, J.M., McDonald, D., Silva-Moreno, B., Veldhoen, N., Helbing, C.C., Hendzel, M.J., Shabanowitz, J., Hunt, D.F., and Ausió, J., Characterization of the histone H2A.Z-1 and H2A.Z-2 isoforms in vertebrates, BMC Biol., 2009, vol. 7, no. 1, p. 86.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Shaytan, A.K., Landsman, D., and Panchenko, A.R., Nucleosome adaptability conferred by sequence and structural variations in histone H2A-H2B dimers, Curr. Opin. Struct. Biol., 2015, vol. 32, pp. 48–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Millar, C.B., Organizing the genome with H2A histone variants, Biochem. J., 2013, vol. 449, no. 3, pp. 567–579.

    Article  CAS  PubMed  Google Scholar 

  24. Draker, R., Ng, M.K., Sarcinella, E., Ignatchenko, V., Kislinger, T., and Cheung, P., A Combination of H2A.Z and H4 acetylation recruits Brd2 to chromatin during transcriptional activation, PLoS Genet., 2012, vol. 8, no. 11, p. e1003047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The research was supported by the Ministry of Science and Higher Education of Russia (grant No. 075-15-2021-1062).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to L. Singhpalchevsk or A. K. Shaytan.

Ethics declarations

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

This work does not contain any studies involving human and animal subjects.

CONFLICT OF INTEREST

The authors of this work declare that they have no conflicts of interest.

Additional information

Translated by A. Barkhash

Publisher’s Note.

Allerton Press remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Singhpalchevsk, L., Shaytan, A.K. Diversity of H2A Histones and Their Effect on Nucleosome Structural Properties. Moscow Univ. Biol.Sci. Bull. 78, 212–218 (2023). https://doi.org/10.3103/S0096392523600734

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S0096392523600734

Keywords:

Navigation