Biology subjects

Edwards, C. A.

Publications and source records attributed to Edwards, C. A..

3 recordsLinked to original sources

bioRxiv2026

Regulatory Mechanisms of Maternal Imprinting at the Dlk1-Dio3 Domain

Genomic imprinting is an epigenetic process causing parent-of-origin specific gene expression. The Dlk1-Dio3 domain is one of the largest imprinted clusters. While DNA methylation at an intergenic CpG-island (IG-CGI) within the imprinting control region (ICR) controls expression from the paternal chromosome, mechanisms regulating the unmethylated maternal chromosome remain unknown. Within the transcriptional regulatory element (IG-TRE) of the ICR, deletions identified a minimal region in vitro exhibiting both silencing and enhancing activity, with SOX2 and ZFP281 contributing to enhancer function on the maternal chromosome. In vivo, however, this deletion did not affect maternal expression in embryos; instead it activated Dlk1 on both parental chromosomes. Combining deletion of this IG-TRE with the lethal IG-CGI deletion rescued lethality by balancing Dlk1 expression, despite persistent maternal gene upregulation. These results demonstrate that loss of expression at this domain is more detrimental than gain highlighting the importance of in vivo analysis. Identification of active regulatory factors on the unmethylated maternal chromosome challenges the prevailing view that imprinting is primarily a methylation-driven phenomenon, further revealing the sophisticated hierarchical mechanisms governing imprinting control.

genetics↗

bioRxiv2024

Olfactory combinatorial coding supports risk-reward decision making in C. elegans

Olfactory-driven behaviors are essential for animal survival, but mechanisms for decoding olfactory inputs remain poorly understood. We have used whole-network Ca++ imaging to study olfactory coding in Caenorhabditis elegans. We show that the odorant 1-octanol is encoded combinatorially in the periphery as both an attractant and a repellant. These inputs are integrated centrally, and their relative strengths determine the sensitivity and valence of the behavioral response through modulation of locomotory reversals and speed. The balance of these pathways also dictates the activity of the locomotory command interneurons, which control locomotory reversals. This balance serves as a regulatory node for response modulation, allowing C. elegans to weigh opportunities and hazards in its environment when formulating behavioral responses. Thus, an odorant can be encoded simultaneously as inputs of opposite valence, focusing attention on the integration of these inputs in determining perception, response, and plasticity.

neuroscience↗

bioRxiv2022

Weak parent-of-origin expression bias: is this imprinting?

In mouse and human, genes subjected to genomic imprinting have been shown to function in development, behaviour, and post-natal adaptations. Failure to correctly imprint genes in human is associated with developmental syndromes, adaptive and metabolic disorders during life as well as numerous forms of cancer. In recent years researchers have turned to RNA-seq technologies applied to reciprocal hybrid strains of mice to identify novel imprinted genes, causing a 3-fold increase in genes reported as having a parental origin specific expression bias. The functional relevance of parental origin-specific expression bias is not fully appreciated especially since many are reported with only minimal parental bias (e.g. 51:49). Here we present an in-depth meta-analysis of previously generated RNA-seq data and show that the methods used to generate and analyse libraries greatly influence the calling of allele-specific expression. Validation experiments show that most novel genes called with parental-origin specific allelic bias are artefactual, with the mouse strain contributing a larger effect on expression biases than parental origin. Of the weak novel genes that do validate, most are located at the periphery of known imprinted domains, suggesting they may be affected by local allele- and tissue-specific conformation. Together these findings highlight the need for robust tools, definitions, and validation of putative imprinted genes to provide meaningful information within imprinting databases and to understand the functional and mechanistic implications of the process.

genomics↗