Arents G

Chen YF

Espagne E

Gad W

Grunstein M

Hepat R

Ibrahim AMA

Kim J

Kim Y

Kuo MH

Kwon B

Luger K

Pazin M

Shogren-Knaak M

Stoltz DB

Theilmann DA

Turner BM

Volkoff AN

Webb B

Webb BA

Whitfield JB

Wolffe AP

Wu RS

Wyder S

ABSTRACT
          
            A viral histone H4 (CpBV-H4) is encoded in a polydnavirus,
            Cotesia plutellae
            bracovirus. Its predicted amino acid sequence is highly homologous to that of host insect histone H4 except for an extended N-terminal tail containing 38 amino acids with nine lysine residues. Its expression induces an immunosuppression of target insects by suppressing immune-associated genes, presumably through an epigenetic control. This study analyzed its molecular interaction with eukaryotic host nucleosomes and subsequent regulation of host gene expression. Purified recombinant CpBV-H4 could associate with nucleosomal components (H2A, H2B, H3, and H4) and form an octamer. Transient expression of CpBV-H4 in an insect,
            Tribolium castaneum
            , was performed by microinjection of a recombinant expression vector and confirmed by both reverse transcriptase PCR (RT-PCR) and immunoblotting assays. Under this transient expression condition, total RNAs were extracted and read by a deep-sequencing technique. Annotated transcripts were classified into different gene ontology (GO) categories and compared with those of control insects injected with a truncated CpBV-H4. Target genes manipulated by CpBV-H4 expression showing significant differences (fold changes &gt; 10
            9
            ) included all GO categories, including development and immune-associated genes. When the target genes were physically mapped, they were found to be scattered on entire chromosomes of
            T. castaneum
            . In addition, chromatin immunoprecipitation against CpBV-H4 determined 16 nucleosome sites (
            P
            &lt; 10
            −5
            ) of the viral histone incorporation, which were noncoding regions near DNA-binding and inducible genes. These findings suggest that the viral histone H4 alters host gene expression by a direct molecular interaction with insect nucleosomes.
          </jats:p

Rahul Hepat

Ji-Joon Song

Daeweon Lee

Yonggyun Kim

Crossref

Journal of Virology

A Viral Histone H4 Joins to Eukaryotic Nucleosomes and Alters Host Gene Expression

A Viral Histone H4 Joins to Eukaryotic Nucleosomes and Alters Host Gene Expression

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