Histones serve to both package and organize DNA within the nucleus. In addition to histone post-translational modification and chromatin remodelling complexes, histone variants contribute to the complexity of epigenetic regulation of the genome. Histone variants are characterized by a distinct protein sequence and a selection of designated chaperone systems and chromatin remodelling complexes that regulate their localization in the genome. In addition, histone variants can be enriched with specific post-translational modifications, which in turn can provide a scaffold for recruitment of variant-specific interacting proteins to chromatin. Thus, through these properties, histone variants have the capacity to endow specific regions of chromatin with unique character and function in a regulated manner. In this Review, we provide an overview of recent advances in our understanding of the contribution of histone variants to chromatin function in mammalian systems. First, we discuss new molecular insights into chaperone-mediated histone variant deposition. Next, we discuss mechanisms by which histone variants influence chromatin properties such as nucleosome stability and the local chromatin environment both through histone variant sequence-specific effects and through their role in recruiting different chromatin-associated complexes. Finally, we focus on histone variant function in the context of both embryonic development and human disease, specifically developmental syndromes and cancer.

The roles of histone variants in fine-tuning chromatin organization and function

Single-Cell Characterization of Malignant Phenotypes and Developmental Trajectories of Adrenal Neuroblastoma

Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation.

MicroRNAs Overcome Cell Fate Barrier by Reducing EZH2-Controlled REST Stability during Neuronal Conversion of Human Adult Fibroblasts.

Advancing therapy for neuroblastoma

ATRX In-Frame Fusion Neuroblastoma Is Sensitive to EZH2 Inhibition via Modulation of Neuronal Gene Signatures.

Background & aims Tufting enteropathy (TE) is a rare congenital disorder often caused by mutations in the gene encoding epithelial cell adhesion molecule (EpCam) The disease leads to diarrhea, intestinal failure and dependence on total parenteral nutrition (TPN) These patients often have liver impairments, but the pathology and mechanism of the damage are not well understood We evaluated liver biopsies from TE patients to understand the pathophysiology Methods We identified three patients with TE who underwent liver biopsy Two normal controls and 45 patients on TPN secondary to short gut syndrome were selected for comparison (5 were age- and TPN duration-matched to the TE patients) Results We found that all TE patients showed a complete loss of EpCam expression in enterocytes and biliary epithelial cells, while the normal and TPN groups show basolateral expression Histologically TE patients showed ductopenia, which was not seen in control groups E-cadherin and β-catenin are normally located along the lateral membrane of biliary epithelial cells However, they were relocated to the apical membrane in TE patients, indicating a defect in the apical-basal polarity of cholangiocytes We examined hepatic reparative cells and found near absence of hepatic progenitor cells and intermediate hepatobiliary cells with mild reactive ductular cells in TE patients Conclusion Our findings show that TE is associated with disrupted polarity of cholangiocyte and ductopenia We demonstrate for the first time a role of EpCam in the maintenance of integrity of biliary epithelium We also provided evidence for a disrupted development of hepatic reparative cells

EpCam is required for maintaining the integrity of the biliary epithelium.

Bacillus cereus is a gram-positive, rod-shaped bacterium that is commonly implicated in foodborne illness but has also become increasingly recognized as a source of serious non-gastrointestinal inf...

Fumiko Dekio

Papers

ATRX In-Frame Fusion Neuroblastoma Is Sensitive to EZH2 Inhibition via Modulation of Neuronal Gene Signatures.

EpCam is required for maintaining the integrity of the biliary epithelium.

Florid Bacillus cereus Infection of the Placenta Associated With Intrauterine Fetal Demise.

Crohn’s-like Enteritis in X-Linked Agammaglobulinemia: A Case Series and Systematic Review