Genetic risk factors for severe and fatigue dominant long COVID and commonalities with ME/CFS identified by combinatorial analysis.

Background: Long COVID is a debilitating chronic condition that has affected over 100 million people globally. It is characterized by a diverse array of symptoms, including fatigue, cognitive dysfunction and respiratory problems. Studies have so far largely failed to identify genetic associations, the mechanisms behind the disease, or any common pathophysiology with other conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) that present with similar symptoms.

H3K27 modifiers regulate lifespan in C. elegans in a context-dependent manner.

Background: Evidence of global heterochromatin decay and aberrant gene expression in models of physiological and premature ageing have long supported the "heterochromatin loss theory of ageing", which proposes that ageing is aetiologically linked to, and accompanied by, a progressive, generalised loss of repressive epigenetic signatures. However, the remarkable plasticity of chromatin conformation suggests that the re-establishment of such marks could potentially revert the transcriptomic architecture of animal cells to a "younger" state, promoting longevity and healthspan. To expand our understanding of the ageing process and its connection to chromatin biology, we screened an RNAi library of chromatin-associated factors for increased longevity phenotypes.

Sense and antisense transcription are associated with distinct chromatin architectures across genes.

Genes from yeast to mammals are frequently subject to non-coding transcription of their antisense strand; however the genome-wide role for antisense transcription remains elusive. As transcription influences chromatin structure, we took a genome-wide approach to assess which chromatin features are associated with nascent antisense transcription, and contrast these with features associated with nascent sense transcription. We describe a distinct chromatin architecture at the promoter and gene body specifically associated with antisense transcription, marked by reduced H2B ubiquitination, H3K36 and H3K79 trimethylation and increased levels of H3 acetylation, chromatin remodelling enzymes, histone chaperones and histone turnover.

Genotoxins induce binucleation in L5178Y and TK6 cells.

Following the initial observation that methyl methanesulphonate induced binucleated cells in the AHH-1 line and a significant number of them contained micronuclei, human lymphoblastoid TK6 and mouse lymphoma L5178Y cells were treated with methyl methanesulphonate, methylnitrosourea, mitomycin C, cytosine arabinoside, colchicine and triton X. All except triton X induced binucleated cells in both lines but an increased micronucleus incidence in them was seen only in TK6. The two lines also differed in the numbers of binucleates in the control cultures with 2.