Disease relevance of His3.3A

• In addition, we showed on immuno blots that two monoclonal antibodies isolated from mice with systemic lupus erythematosus (SLE) display strong reactivity with the H3.3 histone, but not with its replication-dependent counterparts [1].

High impact information on His3.3A

• Here we introduce a new strategy for profiling epigenetic patterns on the basis of H3.3 replacement, using microarrays covering roughly one-third of the Drosophila melanogaster genome at 100-bp resolution [2].
• When chromatin assembly occurs at other times, the histone H3.3 variant replaces canonical H3 [2].
• H3.3 replacement occurred prominently at sites of abundant RNA polymerase II and methylated H3 Lys4 throughout the genome and was enhanced on the dosage-compensated male X chromosome [2].
• We propose that deposition and inheritance of actively modified H3.3 in regulatory regions maintains transcriptionally active chromatin [2].
• In contrast, we find that the Drosophila HSP70 genes rapidly lose histone H3 and acquire variant H3.3 histones as they are induced [3].

Biological context of His3.3A

• H3.3 is also incorporated during decondensation of the Drosophila sperm pronucleus, indicating a direct role in chromatin remodeling upon fertilization [4].
• Strikingly, the X chromosome becomes deficient in H3.3 during gametogenesis, indicating a low level of histone turnover [4].
• A universal histone variant, H3.3, is incorporated at sites of active transcription throughout the cell cycle [4].
• H3.3 patterns are similar to patterns of H3K4 methylation in the primordial germ cells and on the X chromosome during gametogenesis, suggesting that histone turnover and modification are coupled processes [4].
• Transcriptional activation triggers deposition and removal of the histone variant H3.3 [3].

Anatomical context of His3.3A

• In early embryos, H3.3 becomes specifically depleted from primordial germ cells [4].
• Using a Drosophila cell line system in which H3.3 has been shown to specifically package active loci, we found that H3.3 accounts for approximately 25% of total histone 3 in bulk chromatin, enough to package essentially all actively transcribed genes [5].
• Histone H3.3 disappears from the spermatid nuclei, along with the other core histones, during the late stages of spermatogenesis [1].
• The exclusive marking of paternal chromosomes with H3.3 represents a primary epigenetic distinction between parental genomes in the zygote, and underlines an important consequence of the critical and highly specialized function of HIRA at fertilization [6].

Associations of His3.3A with chemical compounds

• To address this uncertainty, we have quantified the relative abundance of H3 and H3.3 and their lysine modifications [5].
• MS and antibody characterization of separated histone 3 fractions revealed that H3.3 is relatively enriched in modifications associated with transcriptional activity and deficient in dimethyl lysine-9, which is abundant in heterochromatin [5].

Other interactions of His3.3A

• Chromatin associated with transcriptionally active loci becomes enriched for histones with particular lysine modifications and accumulates the H3.3 histone variant, the substrate for replication-independent nucleosome assembly [5].
• The histone H3.3 chaperone HIRA is essential for chromatin assembly in the male pronucleus [6].

References