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Okafor, A.

Publications and source records attributed to Okafor, A..

2 recordsLinked to original sources

Transcriptome analysis reveals a novel DNA element that may interact with chromatin-associated proteins in Plasmodium berghei during erythrocytic development

BackgroundThe life cycle of Plasmodium parasites is intricate and multistage, alternating between dynamic environments. Temporal regulation of transcription by stage-specific transcription factor binding at particular regulatory regions within gene promoters facilitates its progression. As a result, each new developmental stage is endowed with its unique gene sets, whose just-in-time expression enables the parasite to completely adapt to the necessary circumstances. Our understanding of these transcriptome-level regulatory processes is limited, and more so, a thorough examination of the entire life cycle in the experimentally tractable rodent model organism P. berghei is lacking. ResultsWe performed a genome-wide analysis of RNA-Seq data from different developmental stages of P. berghei. Integrated data from the human malaria parasites P. falciparum and P. vivax demonstrated that Plasmodium parasites have a unique transcriptional signature. We identified the sets of genes differentially expressed at each stage, clustered them based on similarities of their expression profiles, and predicted the regulatory motifs governing their expression. We interpreted the motifs using known binding sites for established eukaryotic transcription factors, including those of the ApiAP2s, and identified eight potentially novel motifs. Additionally, we expanded the annotation of another motif--AGGTAA--found in genes exclusive to erythrocytic development and identified members of the PfMORC and GCN5 complexes among its possible interacting proteins. ConclusionThis study provides new insights into gene usage and its regulation during P. berghei development.

bioinformatics↗

UBE2N is essential for maintenance of skin homeostasis and suppression of inflammation

UBE2N, a Lys63-ubiquitin conjugating enzyme, plays critical roles in embryogenesis and immune system development and function. However, its roles in adult epithelial tissue homeostasis and pathogenesis are unclear. We generated conditional mouse models that deleted Ube2n in skin cells in a temporally and spatially controlled manner. We found that Ube2n- knockout (KO) in the adult skin keratinocytes induced a range of inflammatory skin defects characteristic of psoriatic and actinic keratosis. These included eczematous inflammation, epidermal and dermal thickening, parakeratosis, and increased immune cell infiltration, as well as signs of edema and blistering. Single cell transcriptomic analyses and RT-qPCR showed that Ube2n KO keratinocytes expressed elevated myeloid cell chemo-attractants such as Cxcl1 and Cxcl2 and decreased the homeostatic T lymphocyte chemo-attractant, Ccl27a. Consistently, the infiltrating immune cells of Ube2n-KO skin were predominantly myeloid-derived cells including neutrophils and M1-like macrophages that were highly inflammatory, as indicated by expression of Il1{beta} and Il24. Pharmacological blockade of the IL-1 receptor associated kinases (IRAK1/4) alleviated eczema, epidermal and dermal thickening, and immune infiltration of the Ube2n mutant skin. Together, these findings highlight a key role of keratinocyte-UBE2N in maintenance of epidermal homeostasis and skin immunity and identify IRAK1/4 as potential therapeutic target for inflammatory skin disorders.

pathology↗