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Summary: Histone H3 lysine‐4 trimethylation (H3K4me3) activating drought‐responsive genes in plants for drought adaptation has long been established, but the underlying regulatory mechanisms are unknown.Here, using yeast two‐hybrid, bimolecular fluorescence complementation, biochemical analyses, transient and CRISPR‐mediated transgenesis in Populus trichocarpa, we unveiled in this adaptation a regulatory interplay between chromatin regulation and gene transactivation mediated by an epigenetic determinant, a PtrSDG2‐1–PtrCOMPASS (complex proteins associated with Set1)‐like H3K4me3 complex, PtrSDG2‐1–PtrWDR5a‐1–PtrRbBP5‐1–PtrAsh2‐2 (PtrSWRA).Under drought conditions, a transcription factor PtrAREB1‐2 interacts with PtrSWRA, forming a PtrSWRA–PtrAREB1‐2 pentamer, to recruit PtrSWRA to specific promoter elements of drought‐tolerant genes, such as PtrHox2, PtrHox46, and PtrHox52, for depositing H3K4me3 to promote and maintain activated state of such genes for tolerance. CRISPR‐edited defects in the pentamer impaired drought tolerance and elevated expression of PtrHox2, PtrHox46, or PtrHox52 improved the tolerance as well as growth in P. trichocarpa.Our findings revealed the identity of the underlying H3K4 trimethyltransferase and its interactive arrangement with the COMPASS for catalysis specificity and efficiency. Furthermore, our study uncovered how the H3K4 trimethyltransferase–COMPASS complex is recruited to the effector genes for elevating H3K4me3 marks for improved drought tolerance and growth/biomass production in plants. [ABSTRACT FROM AUTHOR]

The present study surveyed the characteristics of hepatitis B virus (HBV) integration in the liver genomes of patients with acute hepatitis B (AHB), carriers of inactive hepatitis B surface antigen (HBsAg), and patients with chronic hepatitis B (CHB) receiving antiviral treatment. 'Short-read' whole genome sequencing (WGS) with an average of 4,879× coverage for HBV integration was performed in three patients with AHB, two carriers of inactive HBsAg, and 13 patients with CHB receiving antiviral treatment. Conventional polymerase chain reaction and Sanger sequencing were used to verify integration breakpoints supported by at least two paired-end reads, and viral-host chimeric transcripts were surveyed simultaneously. HBV integration breakpoints were 100% identified with an average of 138.2±379.9 breakpoints per sample. The numbers of HBV integration breakpoints were positively associated with the sequencing depth coverage numbers and levels of intrahepatic covalently closed circular DNA, respectively (P<0.0001 and P<0.0001). Four types of viral-host junction in 14 HBV integration breakpoints were detected (two viral junctions mapped in the HBs gene, one in the Precore gene, and others within the HBx gene): Forward simple junction, reverse simple junction, forward and reverse complicated junction, and microhomology were found in many of the junctions. Expression of viral-human chimeric transcripts was observed in several breakpoints, including the HBs gene. As a result, HBV can integrate into the host gene in the same manner as non-homologous end joining and microhomology-mediated end joining with numerous sites, and a close association may exist between HBV integration and patient prognosis. HBx integration may be indispensable for viral-host chimeric transcription and HBsAg may be produced from integrated DNA. [ABSTRACT FROM AUTHOR]

Plants develop tolerance to drought by activating genes with altered levels of epigenetic modifications. Specific transcription factors are involved in this activation, but the molecular connections within the regulatory system are unclear. Here, we analyzed genome-wide acetylated lysine residue 9 of histone H3 (H3K9ac) enrichment and examined its association with transcriptomes in Populus trichocarpa under drought stress. We revealed that abscisic acid-Responsive Element (ABRE) motifs in promoters of the drought-responsive genes PtrNAC006 , PtrNAC007 , and PtrNAC120 are involved in H3K9ac enhancement and activation of these genes. Overexpressing these PtrNAC genes in P trichocarpa resulted in strong drought-tolerance phenotypes. We showed that the ABRE binding protein PtrAREB1-2 binds to ABRE motifs associated with these PtrNAC genes and recruits the histone acetyltransferase unit ADA2b-GCN5, forming AREB1-ADA2b-GCN5 ternary protein complexes. Moreover, this recruitment enables GCN5-mediated histone acetylation to enhance H3K9ac and enrich RNA polymerase II specifically at these PtrNAC genes for the development of drought tolerance. CRISPR editing or RNA interference-mediated downregulation of any of the ternary members results in highly drought-sensitive P trichocarpa Thus, the combinatorial function of the ternary proteins establishes a coordinated histone acetylation and transcription factor-mediated gene activation for drought response and tolerance in Populus species., (© 2019 American Society of Plant Biologists. All rights reserved.)

This study aimed to investigate the persistence and predictive values of intrahepatic (IH) hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and total DNA (tDNA) in patients with acute hepatitis B (AHB) and patients with chronic hepatitis B (CHB) receiving anti‑viral treatment. The levels of IH cccDNA and tDNA, serum HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and alanine aminotransferase (ALT) were detected in 11 patients with AHB and 46 patients with CHB who were receiving anti‑viral treatment, among whom 21 had primary treatment failure, 11 achieved virological response (VR) and 15 achieved VR and HBsAg seroclearance. The median IH cccDNA and tDNA levels in the patients with AHB (0.002 copies/cell and 0.04 copies/cell, respectively) were significantly lower than those in the patients with CHB. In the patients with CHB, the median IH cccDNA level among individuals who achieved VR and HBsAg seroclearance (0.012 copies/cell) was significantly lower than that in those who had failed primary treatment (4.18 copies/cell, P<0.0001) but not that in those who achieved solely VR (0.039 copies/cell, P=0.169). The median IH tDNA level in patients with CHB who achevied VR and HBsAg seroclearance (0.096 copies/cell) was significantly lower than that in those who failed primary treatment (371 copies/cell, P<0.0001) and those who achieved solely VR (1.62 copies/cell, P=0.001). No significant difference was observed in the area under the receiver operating characteristic (ROC) curve, which was used to predict the likelihood of achieving VR and HBsAg seroclearance, between IH tDNA and IH cccDNA levels (0.96 and 0.88, respectively; P>0.10). IH cccDNA levels were shown to be positively correlated with serum ALT (P=0.024), HBeAg (P=0.001) and IH tDNA levels (P<0.0001), but not with serum HBV DNA (P=0.12) and HBsAg levels in either HBeAg‑positive (P=0.84) or in HBeAg‑negative (P=0.146) patients. In conclusion, IH cccDNA may persist in patients with AHB and patients with CHB who acheive VR and HBsAg seroclearance following anti‑viral treatment. Furthermore, IH cccDNA and tDNA may have potential in predicting successful therapeutic response in patients with CHB who receive anti‑viral treatment.