Non-coding RNA (ncRNA) species, mainly long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been currently imputed for lesser or greater involvement in human erythropoiesis. These RNA subsets operate within a complex circuit with other epigenetic components and transcription factors (TF) affecting chromatin remodeling during cell differentiation. Lymphoma/leukemia-related (LRF) TF exerts higher occupancy on DNA CpG rich sites and is implicated in several differentiation cell pathways and erythropoiesis among them and also directs the epigenetic regulation of hemoglobin transversion from fetal (HbF) to adult (HbA) form by intervening in the γ-globin gene repression. We intended to investigate LRF activity in the evolving landscape of cells’ commitment to the erythroid lineage and specifically during HbF to HbA transversion, to qualify this TF as potential repressor of lncRNAs and miRNAs. Transgenic human erythroleukemia cells, overexpressing LRF and further induced to erythropoiesis, were subjected to expression analysis in high LRF occupancy genetic loci-producing lncRNAs. LRF abundance in genetic loci transcribing for studied lncRNAs was determined by ChIP-Seq data analysis. qPCRs were performed to examine lncRNA expression status. Differentially expressed miRNA pre- and post-erythropoiesis induction were assessed by next-generation sequencing (NGS), and their promoter regions were charted. Expression levels of lncRNAs were correlated with DNA methylation status of flanked CpG islands, and contingent co-regulation of hosted miRNAs was considered. LRF-binding sites were overrepresented in LRF overexpressing cell clones during erythropoiesis induction and exerted a significant suppressive effect towards lncRNAs and miRNA collections. Based on present data interpretation, LRF’s multiplied binding capacity across genome is suggested to be transient and associated with higher levels of DNA methylation. Key messages During erythropoiesis, LRF displays extensive occupancy across genetic loci. LRF significantly represses subsets of lncRNAs and miRNAs during erythropoiesis. Promoter region CpG islands’ methylation levels affect lncRNA expression. MiRNAs embedded within lncRNA loci show differential regulation of expression.

The clinical heterogeneity regarding the response profile of the antitumor necrosis factor (anti-TNF) in patients with Crohn’s disease (CD) and psoriasis (PsO) is attributed, amongst others, to genetic factors that influence the regulatory mechanisms which orchestrate the inflammatory response. Here, we investigated the possible associations between the MIR146A rs2910164 and MIR155 rs767649 variants and the response to anti-TNF therapy in a Greek cohort of 103 CD and 100 PsO patients. We genotyped 103 CD patients and 100 PsO patients via the PCR-RFLP method, utilizing the de novo formation of a restriction site for the SacI enzyme considering the MIR146A rs2910164, while Tsp45I was employed for the MIR155 rs767649 variant. Additionally, we investigated the potential functional role of the rs767649 variant, exploring in silico the alteration of transcription factor binding sites (TFBSs) mapped on its genomic location. Our single-SNP analysis displayed a significant association between the rare rs767649 A allele and response to therapy (Bonferroni-corrected p value = 0.012) in patients with PsO, a result further enhanced by the alteration in the IRF2 TFBS caused by the above allele. Our results highlight the protective role of the rare rs767649 A allele in the clinical remission of PsO, implying its utilization as a pharmacogenetic biomarker.

Despite the increasing research and clinical interest in the predisposition of psoriasis, a chronic inflammatory skin disease, the multitude of genetic and environmental factors involved in its pathogenesis remain unclear. This complexity is further exacerbated by the several cell types that are implicated in Psoriasis’s progression, including keratinocytes, melanocytes and various immune cell types. The observed interactions between the genetic substrate and the environment lead to epigenetic alterations that directly or indirectly affect gene expression. Changes in DNA methylation and histone modifications that alter DNA-binding site accessibility, as well as non-coding RNAs implicated in the post-transcriptional regulation, are mechanisms of gene transcriptional activity modification and therefore affect the pathways involved in the pathogenesis of Psoriasis. In this review, we summarize the research conducted on the environmental factors contributing to the disease onset, epigenetic modifications and non-coding RNAs exhibiting deregulation in Psoriasis, and we further categorize them based on the under-study cell types. We also assess the recent literature considering therapeutic applications targeting molecules that compromise the epigenome, as a way to suppress the inflammatory cutaneous cascade.

Non-coding RNA (ncRNA) species, mainly long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been currently imputed for lesser or greater involvement in human erythropoiesis. These RNA subsets operate within a complex circuit with other epigenetic components and transcription factors (TF) affecting chromatin remodeling during cell differentiation. Lymphoma/Leukemia related (LRF) TF exerts higher occupancy on DNA CpG rich sites and is implicated in several differentiation cell pathways and erythropoiesis among them. Also, directs the epigenetic regulation of hemoglobin transversion from fetal (HbF) to adult (HbA) form by intervening in the γ-globin gene repression. We intended to investigate LRF activity in the evolving landscape of cells’ commitment to the erythroid lineage and specifically during HbF to HbA transversion, to qualify this TF as potential repressor of lncRNAs and miRNAs. Transgenic human erythroleukemia cells, overexpressing LRF and further induced to erythropoiesis, were subjected to expression analysis in high LRF occupancy genetic loci producing lncRNAs. LRF abundance in genetic loci transcribing for studied lncRNAs was determined by ChIP-Seq data analysis. qPCRs were performed to examine lncRNAs expression status. Differentially expressed miRNAs pre- and post-erythropoiesis induction were assessed by next generation sequencing (NGS) and their promoter regions were charted. Expression levels of lncRNAs were correlated with DNA methylation status of flanked CpG islands and contingent co-regulation of hosted miRNAs was considered. LRF binding sites were overrepresented in LRF overexpressing cell clones during erythropoiesis induction and exerted a significant suppressive effect towards lncRNAs and miRNA collections. Based on present data interpretation LRF’s multiplied binding capacity across genome is suggested to be transient and associated with higher levels of DNA methylation.