Human cytomegalovirus extensively alters nuclear organization and the cellular transcriptome, yet understanding of these genome-wide events remains relatively limited. Here, chromatin conformation capture (Hi-C) revealed how cytomegalovirus alters chromosome organization at both large- and small-scales. Nascent transcriptomics further revealed how transcriptional changes correlate with genomic reorganization, while also uncovering infection-induced transcriptional dysregulation that contributes to the induction of neuronal gene signatures in infected fibroblasts.
View Article and Find Full Text PDFHistone chaperones modulate the stability of histones beginning from histone synthesis, through incorporation into DNA, and during recycling during transcription and replication. Following histone removal from DNA, chaperones regulate histone storage and degradation. Here, we demonstrate that UBR7 is a histone H3.
View Article and Find Full Text PDFDelineating how chromosomes fold at length scales beyond one megabase remains obscure relative to smaller-scale folding into TADs, loops, and nucleosomes. We find that rather than simply unfolding chromatin, histone hyperacetylation results in interactions between distant genomic loci separated by tens to hundreds of megabases, even in the absence of transcription. These hyperacetylated "megadomains" are formed by the BRD4-NUT fusion oncoprotein, interact both within and between chromosomes, and form a specific nuclear subcompartment that has elevated gene activity with respect to other subcompartments.
View Article and Find Full Text PDFIn vivo direct conversion of differentiated cells holds promise for regenerative medicine; however, improving the conversion efficiency and producing functional target cells remain challenging. Ectopic Atoh1 expression in non-sensory supporting cells (SCs) in mouse cochleae induces their partial conversion to hair cells (HCs) at low efficiency. Here, we performed single-cell RNA sequencing of whole mouse sensory epithelia harvested at multiple time points after conditional overexpression of Atoh1.
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