Bioessays

Du, Yongming; Qian, Chengmin

doi: 10.1002/bies.202100229pmid: 35092310

Bivalent chromatin with active H3K4me3 and repressive H3K27me3 was initially identified in embryonic stem cells (ESCs) to poise expression of developmental genes upon lineage commitment. Since then, many more different bivalent modifications have been demonstrated in both ESCs and fully differentiated cells. Bivalency not only spatiotemporally controls gene transcription but also acts to fine‐tune the level of transcription during development. Although increasing number of studies demonstrated the functional significance of bivalent chromatin, the molecular connection of bivalent chromatin and transcriptional regulation remains largely elusive. Recently, we showed Spindlin1/C11orf84 complex prefers to recognize the non‐canonical histone H3K4me3K9me3 bivalent mark, which is required for timely ribosomal RNA transcription. Here, we hypothesize the recognition of K4me3 and K9me3 at the same histone tail by Spindlin1/C11orf84 complex may serve as a general mechanism of conversion from a repressed to an active chromatin structure for transcriptional activation.

Chen, Yanfang; Culetto, Emmanuel; Legouis, Renaud

doi: 10.1002/bies.202100271pmid: 35166388

There is a debate regarding the function of Drp1, a GTPase involved in mitochondrial fission, during the elimination of mitochondria by autophagy. A number of experiments indicate that Drp1 is needed to eliminate mitochondria during mitophagy, either by reducing the mitochondrial size or by providing a noncanonical mitophagy function. Yet, other convincing experimental results support the conclusion that Drp1 is not necessary. Here, we review the possible functions for Drp1 in mitophagy and autophagy, depending on tissues, organisms and stresses, and discuss these apparent discrepancies. In this regard, it appears that the reduction of mitochondria size is often required for mitophagy but not always in a Drp1‐dependent manner. Finally, we speculate on Drp1‐independent mitochondrial fission mechanism that may take place during mitophagy and on noncanonical roles, which Drp1 may play such as modulating organelle contact sites dynamic during the autophagosome formation.

doi: 10.1002/bies.202270008pmid: N/A

Datta, Rhea R.; Rister, Jens

doi: 10.1002/bies.202100191pmid: 35195290

In human languages, a palindrome reads the same forward as backward (e.g., ‘madam’). In regulatory DNA, a palindrome is an inverted sequence repeat that allows a transcription factor to bind as a homodimer or as a heterodimer with another type of transcription factor. Regulatory palindromes are typically imperfect, that is, the repeated sequences differ in at least one base pair, but the functional significance of this asymmetry remains poorly understood. Here, we review the use of imperfect palindromes in Drosophila photoreceptor differentiation and mammalian steroid receptor signaling. Moreover, we discuss mechanistic explanations for the predominance of imperfect palindromes over perfect palindromes in these two gene regulatory contexts. Lastly, we propose to elucidate whether specific imperfectly palindromic variants have specific regulatory functions in steroid receptor signaling and whether such variants can help predict transcriptional outcomes as well as the response of individual patients to drug treatments.

doi: 10.1002/bies.202270007pmid: N/A

Kejnovsky, Eduard; Jedlicka, Pavel

doi: 10.1002/bies.202100242pmid: 35112737

There is growing evidence of evolutionary genome plasticity. The evolution of repetitive DNA elements, the major components of most eukaryotic genomes, involves the amplification of various classes of mobile genetic elements, the expansion of satellite DNA, the transfer of fragments or entire organellar genomes and may have connections with viruses. In addition to various repetitive DNA elements, a plethora of large and small RNAs migrate within and between cells during individual development as well as during evolution and contribute to changes of genome structure and function. Such migration of DNA and RNA molecules often results in horizontal gene transfer, thus shaping the whole genomic network of interconnected species. Here, we propose that a high evolutionary dynamism of repetitive genome components is often related to the migration/movement of DNA or RNA molecules. We speculate that the cytoplasm is probably an ideal compartment for such evolutionary experiments.

Blackstone, Neil W.

doi: 10.1002/bies.202200012pmid: N/A

You, Hong; Gordon, Catherine A.; MacGregor, Skye R.; Cai, Pengfei; McManus, Donald P.

doi: 10.1002/bies.202100286pmid: 35142378

CRISPR‐Cas technology accelerates development of fast, accurate, and portable diagnostic tools, typified by recent applications in COVID‐19 diagnosis. Parasitic helminths cause devastating diseases afflicting 1.5 billion people globally, representing a significant public health and economic burden, especially in developing countries. Currently available diagnostic tests for worm infection are neither sufficiently sensitive nor field‐friendly for use in low‐endemic or resource‐poor settings, leading to underestimation of true prevalence rates. Mass drug administration programs are unsustainable long‐term, and diagnostic tools – required to be rapid, specific, sensitive, cost‐effective, and user‐friendly without specialized equipment and expertise – are urgently needed for rapid mapping of helminthic diseases and monitoring control programs. We describe the key features of the CRISPR‐Cas12/13 system and emphasise its potential for the development of effective tools for the diagnosis of parasitic and other neglected tropical diseases (NTDs), a key recommendation of the NTDs 2021–2030 roadmap released by the World Health Organization.

Newham, Elis; Gill, Pamela G.; Corfe, Ian J.

doi: 10.1002/bies.202100060pmid: 35170781

We suggest that mammalian endothermy was established amongst Middle Jurassic crown mammals, through reviewing state‐of‐the‐art fossil and living mammal studies. This is considerably later than the prevailing paradigm, and has important ramifications for the causes, pattern, and pace of physiological evolution amongst synapsids. Most hypotheses argue that selection for either enhanced aerobic activity, or thermoregulation was the primary driver for synapsid physiological evolution, based on a range of fossil characters that have been linked to endothermy. We argue that, rather than either alternative being the primary selective force for the entirety of endothermic evolution, these characters evolved quite independently through time, and across the mammal family tree, principally as a response to shifting environmental pressures and ecological opportunities. Our interpretations can be tested using closely linked proxies for both factors, derived from study of fossils of a range of Jurassic and Cretaceous mammaliaforms and early mammals.

Marasco, Valeria; Smith, Steve; Angelier, Frédéric

doi: 10.1002/bies.202100184pmid: 35122449

Although early‐life adversity has been associated with negative consequences during adulthood, growing evidence shows that such adversity can also lead to subsequent stress resilience and positive fitness outcomes. Telomere dynamics are relevant in this context because of the link with developmental conditions and longevity. However, few studies have assessed whether the effects of early‐life adversity on developmental telomere dynamics may relate to adult telomere dynamics. We propose that the potential links between early‐life adversity and adult telomere dynamics could be driven by developmental constraints (the Constraint hypothesis), by the nature/severity of developmental adversity (the Resilience hypothesis), or by developmental‐mediated changes in individual life‐history strategies (the Pace of Life hypothesis). We discuss these non‐mutually exclusive hypotheses, explore future research directions, and propose specific studies to test these hypotheses. Our article aims to expand our understanding of the evolutionary role of developmental conditions on adult telomere dynamics, stress resilience and ageing.