No abstract

Dear Editor,COVID-19 has an extremely variable prognosis, ranging from asymptomatic and mildly affected individuals to severe disease and death. We have investigated the transcriptional changes in 36 COVID-19 positive Indian patients hospitalized during the first surge (Figure 1A, Table S1, and Supplementary Methods) against 5 COVID-19 negative samples. RNA was isolated from naso/oropharyngeal swabs for paired end sequencing using the Illumina Nova-seq 6000. We identified 251 upregulated (220 protein coding) and 9068 downregulated (3252 protein coding) differentially expressed genes (DEGs) (adjusted p-value < 0.05 and absolute log2 fold change > 1) (Figure 1B, Tables S2 and S3). Seven patients were critical and required intensive care unit (ICU) intervention, while 23 were discharged from COVID-19 ward (W), although no significant differences could be seen in their transcriptional profiles (Figure 1C). The overall transcriptional reduction, irrespective of disease severity (Figure 1C), is well correlated with the phenomenon of fading host cell functionality and prominent viral protein synthesis, and may be associated with interference in host cellular processes and responses. 1 The results indicate a diverse transcriptomic profile in response to SARS-CoV-2, in line with the variable prognosis seen in many COVID-19 patients. However, we find robust activation of the innate immune response concomitant with a reduction in the gene expression profiles associated with cardiac, muscular, and neurological processes, as well as peripheral neurosensory markers.Immune response genes were highly upregulated (Figure 2A and Table S4), with prominent clusters of genes associated with multiple viral infections (Figure 2B and Table S5) marking the activation of infection clearance pathways. Meta-analysis of published datasets identified a signature of 19 upregulated genes (Table S6), linking Type I interferon (IFN) signaling, host defense, and innate immune responses in SARS-CoV-2 infection (Fig-This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Background Transcription of genes residing within constitutive heterochromatin is paradoxical to the tenets of epigenetic code. The regulatory mechanisms of Drosophila melanogaster heterochromatic gene transcription remain largely unknown. Emerging evidence suggests that genome organization and transcriptional regulation are inter-linked. However, the pericentromeric genome organization is relatively less studied. Therefore, we sought to characterize the pericentromeric genome organization and understand how this organization along with the pericentromeric factors influences heterochromatic gene expression. Results Here, we characterized the pericentromeric genome organization in Drosophila melanogaster using 5C sequencing. Heterochromatic topologically associating domains (Het TADs) correlate with distinct epigenomic domains of active and repressed heterochromatic genes at the pericentromeres. These genes are known to depend on the heterochromatic landscape for their expression. However, HP1a or Su(var)3-9 RNAi has minimal effects on heterochromatic gene expression, despite causing significant changes in the global Het TAD organization. Probing further into this observation, we report the role of two other chromatin proteins enriched at the pericentromeres-dMES-4 and dADD1 in regulating the expression of a subset of heterochromatic genes. Conclusions Distinct pericentromeric genome organization and chromatin landscapes maintained by the interplay of heterochromatic factors (HP1a, H3K9me3, dMES-4 and dADD1) are sufficient to support heterochromatic gene expression despite the loss of global Het TAD structure. These findings open new avenues for future investigations into the mechanisms of heterochromatic gene expression.