Biology subjects

Serizay, J.

Publications and source records attributed to Serizay, J..

7 recordsLinked to original sources

bioRxiv2026

Chromatin is dispensable for bacterial life

Inside cells, DNA is intimately associated with proteins, forming chromatin. The protein constituents of chromatin vary across the tree of life: histones are the principal building blocks of chromatin in eukaryotes and many archaea, whereas bacteria typically encode a collection of nucleoid-associated proteins (NAPs) that wrap, bend, bridge or coat the DNA. Although chromatin proteins appear to be a universal feature of cellular life, DNA-templated processes such as transcription, replication, and DNA repair can take place in vitro in the absence of chromatin, raising the possibility that cellular systems might exist -- or could be built -- that lack chromatin proteins. To explore this possibility, the molecular consequences and potential systemic adjustments required for life without chromatin, we serially deleted the nine most abundant NAPs from E. coli (hupA , hupB , ihfA , ihfB , hns , stpA , fis , dps , lrp), resulting in a strain ({Delta}NAP9) that lacks its native chromatin. Using an array of different techniques, we document change -- and sometimes surprising lack thereof -- in compaction, composition and 3D architecture of the nucleoid, supercoiling, prophage activity, growth, viability, and genetic make-up of {Delta}NAP9. Most notably, we find that {Delta}NAP9 exhibits global dysregulation of gene expression, marked by a striking homogenization of transcriptional output across the genome that is reminiscent of the effects of histone depletion in eukaryotic cells. Our results reinforce the notion that chromatin plays a key role in compartmentalizing the use of genomic information, enabling both the localized suppression of selfish elements and dynamic reprogramming of genome activity in response to environmental change. At the same time, the successful construction of {Delta}NAP9 demonstrates that bacterial cells can carry out basic cellular functions in the absence of co-evolved chromatin proteins, highlighting the potential for radical (re-)engineering of prokaryotic chromatin and systems of gene expression.

microbiology↗

bioRxiv2024

Micro-C reveals MORC/ApiAP2-mediated links between distant, functionally related genes in the human malaria parasite

Genome organization plays a significant role in silencing heterochromatinized genes in the most virulent human malaria parasite, Plasmodium falciparum. However, it remains unclear how heterochromatinized genes spatially cluster or if active genes are also organized in a specific manner. We used Micro-C to achieve a near-nucleosome resolution DNA-DNA contact map, which revealed new inter- and intrachromosomal heterochromatic and euchromatic structures in the blood stage parasite. We observed subtelomeric fold structures that facilitate interactions amongst heterochromatinized genes involved in antigenic variation. In addition, we identified long-range intra- and interchromosomal interactions amongst active, stage-specific genes. Both structures are mediated by AP2-P, an ApiAP2 transcription factor, and a putative MORC chromatin remodeler, and functional specificity is achieved via combinatorial binding with other sequence-specific DNA-binding factors. This study provides unprecedented insight into the organizational machinery used by this medically important eukaryotic parasite to spatially coordinate genes underlying antigenic variation and to co-activate stage-specific genes.

molecular biology↗

bioRxiv2024

Identification of a new cell cycle variant during multiciliated cell differentiation

2A complex and conserved regulatory network drives the cell cycle. Individual components of this network are sometimes used in differentiated cells, i.e. to control organelle destruction in mammalian lens cells or light response in land plants. Some differentiated cells co-opt cell-cycle regulators more largely, to increase their ploidy using a cell cycle variant named endoreplication. Using single-cell RNA-seq profiling and functional assays in differentiating multiciliated cells, we identified a novel type of cell cycle variant that supports cytoplasmic organelle, rather than nuclear content amplification. This variant operates in post-mitotic, centriole-amplifying differentiating multiciliated cells and is characterized by (i) a circular trajectory of the transcriptome, (ii) sequential expression of more than 70% of the genes involved in S, G2 and M-like progression along this trajectory, and (iii) successive waves of cyclins. This cell cycle variant is tailored by the expression of the non-canonical cyclins O and A1 - which replace the transcriptionally silent cyclins E2 and A2 - and by the silencing of the APC/C inhibitor Emi1, two switches also detected in male meiosis, another variant of the canonical cell cycle where centriole and DNA replications are uncoupled. Re-expressing Cyclin E2, cyclin A2 or Emi1 is sufficient to induce partial replication and mitosis, suggesting that change in the regulation of expression of a few cell cycle key players drives a qualitative and quantitative tuning of Cdk activity, allowing the diversion of the cell cycle in the multiciliation variant. We also propose that this new cell cycle variant relies on the existence of a cytoplasmic - or centriolar - Cdk threshold, lower than the S-phase threshold, which affects only the cytoplasmic reorganization. One-Sentence SummaryMCC progenitors undergo a final, tailored iteration of the cell cycle during differentiation, to drive centriole amplification without DNA replication or mitosis.

cell biology↗

bioRxiv2022

Exogenous chromosomes reveal how sequence composition drives chromatin assembly, activity, folding and compartmentalization

Genomic sequences co-evolve with DNA-associated proteins to ensure the multiscale folding of long DNA molecules into functional chromosomes. In eukaryotes, different molecular complexes organize the chromosomes hierarchical structure, ranging from nucleosomes and cohesin- mediated DNA loops to large scale chromatin compartments. To explore the relationships between the DNA sequence composition and the spontaneous loading and activity of these DNA-associated complexes in the absence of co-evolution, we characterized chromatin assembly and activity in yeast strains carrying exogenous bacterial chromosomes that diverged from eukaryotic sequences over 1.5 billion years ago. We show that nucleosome assembly, transcriptional activity, cohesin-mediated looping, and chromatin compartmentalization can occur in a bacterial chromosome with a largely divergent sequence integrated in a eukaryotic host, and that the chromatinization of bacterial chromosomes is highly correlated with their sequence composition. These results are a step forward in understanding how foreign sequences are interpreted by a host nuclear machinery during natural horizontal gene transfers, as well as in synthetic genomics projects.

genetics↗

bioRxiv2020

An Xist-dependent protein assembly mediates Xist localization and gene silencing

Nuclear compartments play diverse roles in regulating gene expression, yet the molecular forces and components driving compartment formation are not well understood. Studying how the lncRNA Xist establishes the inactive-X-chromosome (Xi)-compartment, we found that the Xist RNA-binding-proteins PTBP1, MATR3, TDP43, and CELF1 form a condensate to create an Xi-domain that can be sustained in the absence of Xist. The E-repeat-sequence of Xist serves a multivalent binding-platform for these proteins. Without the E-repeat, Xist initially coats the X-chromosome during XCI onset but subsequently disperses across the nucleus with loss of gene silencing. Recruitment of PTBP1, MATR3, TDP-43 or CELF1 to {Delta}E-Xist rescues these phenotypes, and requires both self-association of MATR3 and TDP-43 and a heterotypic PTBP1-MATR3-interaction. Together, our data reveal that Xist sequesters itself within the Xi-territory and perpetuates gene silencing by seeding a protein-condensate. Our findings uncover an unanticipated mechanism for epigenetic memory and elucidate the interplay between RNA and RNA-binding-proteins in creating compartments for gene regulation.

molecular biology↗

bioRxiv2020

Tissue-specific profiling reveals distinctive regulatory architectures for ubiquitous, germline and somatic genes

Despite increasingly detailed knowledge of gene expression patterns, the regulatory architectures that drive them are not well understood. To address this, we compared transcriptional and regulatory element activities across five adult tissues of C. elegans, covering [~]90% of cells, and defined regulatory grammars associated with ubiquitous, germline and somatic tissue-specific gene expression patterns. We find architectural features that distinguish two major promoter types. Germline-specific and ubiquitously-active promoters have well positioned +1 and -1 nucleosomes associated with a periodic 10-bp WW signal. Somatic tissue-specific promoters lack these features, have wider nucleosome depleted regions, and are more enriched for core promoter elements, which surprisingly differ between tissues. A 10-bp periodic WW signal is also associated with +1 nucleosomes of ubiquitous promoters in fly and zebrafish but is not detected in mouse and human. Our results demonstrate fundamental differences in regulatory architectures of germline-active and somatic tissue-specific genes and provide a key resource for future studies.

genomics↗

bioRxiv2018

Chromatin accessibility dynamics across C. elegans development and ageing

An essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one C. elegans stage. Based on nuclear transcription profiles, we define 15,714 protein-coding promoters and 19,231 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, hundreds of promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements is regulated during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across C. elegans life provides a platform for understanding how transcription controls development and ageing.

genomics↗