Biology subjects

Nabila, A.

Publications and source records attributed to Nabila, A..

3 recordsLinked to original sources

bioRxiv2025

Prenatal adversity configures a subpopulation of ventral dentate granule cells for recruitment to drive innate anxiety

Adverse prenatal environment is a risk factor for the development of psychiatric disorders. Although studies have implicated epigenetic mechanisms, little is known about how epigenomic changes come about and lead to abnormal behaviors in affected individuals. We sought to identify epigenomic and transcriptomic signatures induced by a proinflammatory gestational environment in the ventral dentate gyrus (vDG), a hippocampal region linked to avoidance of threatening contexts, that persist and promote anxiety-like behavior in mice. Here we show that adversity shifted the methylation of enhancers and promoters with intermediate methylation and altered synapse-related gene expression, resulting in epigenetic and transcriptional heterogeneity in the vDG. Exposure to an anxiogenic environment recruited vDG neurons with the most transcriptional alterations. Differentially expressed synapse-relevant genes in ensemble neurons tended to be differentially methylated. Finally, this ensemble exhibited higher activity in threatening than safe environment suggesting a prenatal adversity-induced epigenetic and neurobiological sequence that leads to anxiety.

neuroscience↗

bioRxiv2023

A transposase-derived gene required for human brain development

DNA transposable elements and transposase-derived genes are present in most living organisms, including vertebrates, but their function is largely unknown. PiggyBac Transposable Element Derived 5 (PGBD5) is an evolutionarily conserved vertebrate DNA transposase-derived gene with retained nuclease activity in human cells. Vertebrate brain development is known to be associated with prominent neuronal cell death and DNA breaks, but their causes and functions are not well understood. Here, we show that PGBD5 contributes to normal brain development in mice and humans, where its deficiency causes disorder of intellectual disability, movement, and seizures. In mice, Pgbd5 is required for the developmental induction of post-mitotic DNA breaks and recurrent somatic genome rearrangements. In the brain cortex, loss of Pgbd5 leads to aberrant differentiation and gene expression of distinct neuronal populations, including specific types of glutamatergic neurons, which explains the features of PGBD5 deficiency in humans. Thus, PGBD5 might be a transposase-derived enzyme required for brain development in mammals. One-Sentence SummaryPiggyBac Transposable Element Derived 5 (PGBD5) is required for brain development in humans and mice through genetic and epigenetic mechanisms.

neuroscience↗

bioRxiv2019

Epigenetically bistable regions across neuron-specific genes govern neuron eligibility to a coding ensemble in the hippocampus

Episodic memories are stored in distributed neurons but how eligibility of individual neurons to coding ensembles is determined remains elusive. We identified thousands of predominantly bistable (CpG methylated or unmethylated) regions within neuronal gene bodies, established during the development of the mouse hippocampal dentate gyrus. Reducing DNA methylation and the proportion of the methylated epialleles at bistable regions compromised novel context-induced neuronal activation and spatial memory. Conversely, increasing methylation and the frequency of the methylated epialleles at bistable regions enhanced intrinsic excitability and spatial memory but impaired spatial working memory, indicating that the developmentally established methylated-unmethylated epiallelic balance at bistable regions is essential for proper neuronal excitability and hippocampal cognitive functions. Single-nucleus profiling revealed the enrichment of specific epialleles from a subset of bistable regions, primarily exonic, in encoding neurons. We propose a model in which epigenetically bistable regions create neuron heterogeneity, and specific constellations of exonic epialleles dictate, via modulating neuronal excitability, eligibility to a coding ensemble.

neuroscience↗