Histone H2A.Z explained

Histone H2A.Z is a protein encoded by the H2AZ1 gene in humans.^{[1] [2]}

Function

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 base pairs(bp) of DNA wrapped around a histone octamer, which includes pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted by the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. The H2AFZ gene encodes a replication-independent member of the histone H2A family that is distinct from other members of the family.

Biological Importance

Studies in mice have shown that this particular histone is required for embryonic development and indicate that lack of functional histone H2A leads to embryonic lethality.

Histone H2AZ is a variant of histone H2A, and is used to mediate the thermosensory response, and is essential to perceive the ambient temperature. Nucleosome occupancy of H2A.Z decreases with temperature, and in vitro assays show that H2A.Z-containing nucleosomes wrap DNA more tightly than canonical H2A nucleosomes in Arabidopsis.(Cell 140: 136–147, 2010) However, some of the other studies (Nat. Genet. 41, 941–945 and Genes Dev., 21, 1519–1529) have shown that incorporation of H2A.Z in nucleosomes, when it co-occurs with H3.3, makes them weaker.

Gene Expression and Chromatin Structure

The positioning of H2A.Z containing nucleosomes around transcription start sites has been shown to affect the downstream gene expression.^[3] Recent evidence also points to a role for H2A.Z in repressing a subset of ncRNAs, derepressing CUTs, as well as mediation higher order chromatin structure formation.^[4]

Further reading

• Jason LJ, Moore SC, Lewis JD, etal . Histone ubiquitination: a tagging tail unfolds? . BioEssays . 24 . 2 . 166–74 . 2002 . 11835281 . 10.1002/bies.10038. 39905043 .
• Hatch CL, Bonner WM . Sequence of cDNAs for mammalian H2A.Z, an evolutionarily diverged but highly conserved basal histone H2A isoprotein species . Nucleic Acids Res. . 16 . 3 . 1113–24 . 1988 . 3344202 . 10.1093/nar/16.3.1113 . 334740.
• Kato S, Sekine S, Oh SW, etal . Construction of a human full-length cDNA bank . Gene . 150 . 2 . 243–50 . 1995 . 7821789 . 10.1016/0378-1119(94)90433-2.
• Hatch CL, Bonner WM . Characterization of the proximal promoter of the human histone H2A.Z gene . DNA Cell Biol. . 14 . 3 . 257–66 . 1995 . 7880446 . 10.1089/dna.1995.14.257 . Submitted manuscript.
• Popescu N, Zimonjic D, Hatch C, Bonner W . Chromosomal mapping of the human histone gene H2AZ to 4q24 by fluorescence in situ hybridization . Genomics . 20 . 2 . 333–5 . 1994 . 8020992 . 10.1006/geno.1994.1182 . Submitted manuscript.
• Hatch CL, Bonner WM . An upstream region of the H2AZ gene promoter modulates promoter activity in different cell types . Biochim. Biophys. Acta . 1305 . 1–2 . 59–62 . 1996 . 8605251 . 10.1016/0167-4781(95)00223-5.
• El Kharroubi A, Piras G, Zensen R, Martin MA . Transcriptional Activation of the Integrated Chromatin-Associated Human Immunodeficiency Virus Type 1 Promoter . Mol. Cell. Biol. . 18 . 5 . 2535–44 . 1998 . 9566873 . 10.1128/mcb.18.5.2535 . 110633.
• Slachta CA, Jeevanandam V, Goldman B, etal . Coronary arteries from human cardiac allografts with chronic rejection contain oligoclonal T cells: persistence of identical clonally expanded TCR transcripts from the early post-transplantation period (endomyocardial biopsies) to chronic rejection (coronary arteries) . J. Immunol. . 165 . 6 . 3469–83 . 2000 . 10975868 . 10.4049/jimmunol.165.6.3469. free.
• Pasqualucci L, Neri A, Baldini L, etal . BCL-6 mutations are associated with immunoglobulin variable heavy chain mutations in B-cell chronic lymphocytic leukemia . Cancer Res. . 60 . 20 . 5644–8 . 2000 . 11059755.
• Deng L, de la Fuente C, Fu P, etal . Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated HIV-1 genome and enhances binding to core histones . Virology . 277 . 2 . 278–95 . 2001 . 11080476 . 10.1006/viro.2000.0593 . free.
• Suto RK, Clarkson MJ, Tremethick DJ, Luger K . Crystal structure of a nucleosome core particle containing the variant histone H2A.Z . Nat. Struct. Biol. . 7 . 12 . 1121–4 . 2001 . 11101893 . 10.1038/81971. 5966635 .
• Bräuninger A, Yang W, Wacker HH, etal . B-cell development in progressively transformed germinal centers: similarities and differences compared with classical germinal centers and lymphocyte-predominant Hodgkin disease . Blood . 97 . 3 . 714–9 . 2001 . 11157489 . 10.1182/blood.V97.3.714. free .
• Yamamoto K, Sugita N, Kobayashi T, etal . Evidence for a novel polymorphism affecting both N-linked glycosylation and ligand binding of the IgG receptor IIIB (CD16) . Tissue Antigens . 57 . 4 . 363–6 . 2001 . 11380948 . 10.1034/j.1399-0039.2001.057004363.x. free .
• Faast R, Thonglairoam V, Schulz TC, etal . Histone variant H2A.Z is required for early mammalian development . Curr. Biol. . 11 . 15 . 1183–7 . 2001 . 11516949 . 10.1016/S0960-9822(01)00329-3 . free. 2001CBio...11.1183F .
• Deng L, Wang D, de la Fuente C, etal . Enhancement of the p300 HAT activity by HIV-1 Tat on chromatin DNA . Virology . 289 . 2 . 312–26 . 2001 . 11689053 . 10.1006/viro.2001.1129 . free.
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241. 2002PNAS...9916899M . free .
• Rangasamy D, Berven L, Ridgway P, Tremethick DJ . Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development . EMBO J. . 22 . 7 . 1599–607 . 2003 . 12660166 . 10.1093/emboj/cdg160 . 152904.
• Lusic M, Marcello A, Cereseto A, Giacca M . Regulation of HIV-1 gene expression by histone acetylation and factor recruitment at the LTR promoter . EMBO J. . 22 . 24 . 6550–61 . 2004 . 14657027 . 10.1093/emboj/cdg631 . 291826.

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Histone H2A.Z

Notes and References

1. Hatch CL, Bonner WM . The human histone H2A.Z gene. Sequence and regulation . J Biol Chem . 265 . 25 . 15211–8 . Oct 1990 . 10.1016/S0021-9258(18)77243-8 . 1697587. free .
2. Web site: Entrez Gene: H2AFZ H2A histone family, member Z .
3. Bargaje R., Alam P., Patowary A., Sarkar M., Ali T., Gupta S., Garg M., Singh M., Purkanti R., Scaria V., Sivasubbu S., Brahmachari V., Pillai B. (2012) Proximity of H2A.Z containing nucleosome to the transcription start site influences gene expression levels in the mammalian liver and brain. Nucleic Acids Research (Epub ahead of print)22821566 . 10.1093/nar/gks665 . 3467062 . 40 . 18 . Proximity of H2A.Z containing nucleosome to the transcription start site influences gene expression levels in the mammalian liver and brain . October 2012 . 8965–78 . Bargaje R, Alam MP, Patowary A, etal . Nucleic Acids Research.
4. 10.1016/j.celrep.2015.10.030 . 13 . Chromatin Dynamics and the RNA Exosome Function in Concert to Regulate Transcriptional Homeostasis . 2015 . Cell Reports . 1610–1622 . Rege M . 8 . 26586442 . 4662874 . free.