The control of transcriptional memory by stable mitotic bookmarking.

To maintain cellular identities during development, gene expression profiles must be faithfully propagated through cell generations. The reestablishment of gene expression patterns upon mitotic exit is mediated, in part, by transcription factors (TF) mitotic bookmarking. However, the mechanisms and functions of TF mitotic bookmarking during early embryogenesis remain poorly understood. In this study, taking advantage of the naturally synchronized mitoses of Drosophila early embryos, we provide evidence that GAGA pioneer factor (GAF) acts as a stable mitotic bookmarker during zygotic genome activation. We show that, during mitosis, GAF remains associated to a large fraction of its interphase targets, including at cis-regulatory sequences of key developmental genes with both active and repressive chromatin signatures. GAF mitotic targets are globally accessible during mitosis and are bookmarked via histone acetylation (H4K8ac). By monitoring the kinetics of transcriptional activation in living embryos, we report that GAF binding establishes competence for rapid activation upon mitotic exit.

TopBP1 assembles nuclear condensates to switch on ATR signaling.

ATR checkpoint signaling is crucial for cellular responses to DNA replication impediments. Using an optogenetic platform, we show that TopBP1, the main activator of ATR, self-assembles extensively to yield micrometer-sized condensates. These opto-TopBP1 condensates are functional entities organized in tightly packed clusters of spherical nano-particles. TopBP1 condensates are reversible, occasionally fuse, and co-localize with TopBP1 partner proteins. We provide evidence that TopBP1 condensation is a molecular switch that amplifies ATR activity to phosphorylate checkpoint kinase 1 (Chk1) and slow down replication forks. Single amino acid substitutions of key residues in the intrinsically disordered ATR activation domain disrupt TopBP1 condensation and consequently ATR/Chk1 signaling. In physiologic salt concentration and pH, purified TopBP1 undergoes liquid-liquid phase separation in vitro. We propose that the actuation mechanism of ATR signaling is the assembly of TopBP1 condensates driven by highly regulated multivalent and cooperative interactions.

African Children Vulnerabilities in COVID-19 Era: A Review.

The pandemic of COVID-19 has spread from China to the whole world. Here we address the vulnerability of African children in the context of this health crisis. Based on medical, socio-economic and anthropological studies, we present a thematic review that examines the issue at three levels. Firstly, we address the question of the effect of the virus on children in regard to strategies implemented to limit its spread and the capacity of medical devices in Africa. Second, we address the issue of the additional disruptions that the virus could generate by infecting the parents or guardians of children who often find themselves subject to the disquietudes of an informal economy. Finally, we discuss the long-term effects of the crisis on children about food security issues, particularly in relation to overweight and obesity. Based on studies that have documented the long-term overweight risks that can occur due to school cessation as a result of lockdown measures, we provide strategies to address this emerging public health problem in Africa. We conclude the study by suggesting that all these forms of vulnerabilities remain proactive areas of work to better prepare Africa for future pandemics.