Abstract Background Gene regulation through cis -regulatory elements plays a crucial role in development and disease. A major aim of the post-genomic era is to be able to read the function of cis -regulatory elements through scrutiny of their DNA sequence. Whilst comparative genomics approaches have identified thousands of putative regulatory elements, our knowledge of their mechanism of action is poor and very little progress has been made in systematically de-coding them. Results Here, we identify ancient functional signatures within vertebrate conserved non-coding elements (CNEs) through a combination of phylogenetic footprinting and functional assay, using genomic sequence from the sea lamprey as a reference. We uncover a striking enrichment within vertebrate CNEs for conserved binding-site motifs of the Pbx-Hox hetero-dimer. We further show that these predict reporter gene expression in a segment specific manner in the hindbrain and pharyngeal arches during zebrafish development. Conclusions These findings evoke an evolutionary scenario in which many CNEs evolved early in the vertebrate lineage to co-ordinate Hox-dependent gene-regulatory interactions that pattern the vertebrate head. In a broader context, our evolutionary analyses reveal that CNEs are composed of tightly linked transcription-factor binding-sites (TFBSs), which can be systematically identified through phylogenetic footprinting approaches. By placing a large number of ancient vertebrate CNEs into a develo

The skin, the largest organ of the human body, plays numerous essential roles, including protection against environmental hazards and the regulation of body temperature. The processes of skin homeostasis and ageing are complex and influenced by many factors, with epigenetic mechanisms being particularly significant. Epigenetics refers to the regulation of gene expression without altering the underlying DNA sequence. The dynamic nature of the skin, characterized by constant cellular turnover and responsiveness to environmental stimuli, requires precise gene activity control. This control is largely mediated by epigenetic modifications such as DNA methylation, histone modification, and regulation by non-coding RNAs. The present review endeavours to provide a comprehensive exploration and elucidation of the role of epigenetic mechanisms in regulating skin homeostasis and ageing. By integrating our current knowledge of epigenetic modifications with the latest advancements in dermatological research, we can gain a deeper comprehension of the complex regulatory networks that govern skin biology. Understanding these mechanisms also presents promising avenues for therapeutic interventions aimed at improving skin health and mitigating age-related skin conditions.

Background: Gene regulation through cis-regulatory elements plays a crucial role in development and disease. A major aim of the post-genomic era is to be able to read the function of cis-regulatory elements through scrutiny of their DNA sequence. Whilst comparative genomics approaches have identified thousands of putative regulatory elements, our knowledge of their mechanism of action is poor and very little progress has been made in systematically de-coding them. Results: Here, we identify ancient functional signatures within vertebrate conserved non-coding elements (CNEs) through a combinati

DNA methylation plays a crucial role in the establishment of tissue-specific gene expression and the regulation of key biological processes. However, our present inability to predict the effect of genome sequence variation on DNA methylation precludes a comprehensive assessment of the consequences of non-coding variation. We introduce CpGenie, a sequence-based framework that learns a regulatory code of DNA methylation using a deep convolutional neural network and uses this network to predict the impact of sequence variation on proximal CpG site DNA methylation. CpGenie produces allele-specific

Non-coding DNA constitutes the vast majority of eukaryotic genomes, yet its evolutionary role remains largely unresolved. This manuscript proposes a theoretical model in which non-coding DNA persists not due to functional utility, but as "passive selfish DNA"—elements that replicate by coexisting with coding sequences in vital genomes. Drawing analogies with endogenous retroviruses and vertically transmitted transposons, this perspective reframes the issue of genomic persistence in terms of replicative neutrality and genomic compatibility rather than function. The model suggests new directions for investigating genome architecture and evolutionary neutrality.

Following the completion of the Human Genome Project, which revealed that the number of the protein-coding genes in human and mouse is nearly the same, many researchers began to be interested in non-coding RNAs, which are transcribed from so-called ‘‘junk DNA’’, a name suggesting these are no more than genomic garbage. This genomic region does not code protein, and shows considerable interspecies and inter-individual diversity, suggesting that it has the potential to be key to explaining the difference between human and mice, and between human individuals. Early studies focused on small RNAs i

Highly homologous sequences 154-157 bp in length grouped under the name of "conserved non-protein-coding element" (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.

Neurodegenerative diseases have a significant impact on individuals and society. The exact causes of these diseases are not fully understood, but evidence suggests that a combination of genetic, environmental, and lifestyle factors contribute to their development. Methods: This narrative review explores the role of epigenetic regulation in gene expression during the development of neurodegenerative diseases. An exhaustive literature search was conducted using electronic databases, and articles focusing on epigenetic regulation in the context of neurodegenerative diseases were selected for anal

Transcription-associated RNA surveillance is vital to the well-being of the cell by processing both coding and noncoding RNA (ncRNA). When left unregulated, RNA transcripts can cause genomic instability by forming structures called R-loops that leave a single strand of DNA exposed to potentially harmful events like nicks and mutations. The RNA exosome is the 3’ exoribonuclease that plays an important role in degrading both coding and ncRNA, and its role in processing ncRNA transcripts has been demonstrated extensively in the recent past. The role of ncRNA transcription and the RNA exosome is b

The activation of the epithelial-mesenchymal transition (EMT) enhances cell plasticity and plays a pivotal role in driving critical biological processes such as embryonic process, tissue repair, and cancer metastasis. EMT is regulated by multiple signaling pathways, including transforming growth factor-β (TGF-β), Wnt, and Notch signaling, and is finely orchestrated by a network of transcriptional factors, epigenetic modifications (such as DNA methylation and histone alterations), and non-coding RNAs. In the peripheral nervous system, Schwann cells undergo a distinct EMT-like transformation following nerve injury, adopting a repair phenotype known as repair Schwann cells. These repair Schwann cells play a multifaceted role in nerve regeneration by clearing myelin debris, secreting regeneration-promoting factors, mediating structural reorganization, and creating a conducive microenvironment for axonal regrowth. Therapeutic strategies targeting the regulation of the EMT-like program of Schwann cells thus hold significant promise for the treatment of peripheral nerve injury, particularly in cases of severe nerve injury with incomplete recovery and poor functional restoration.

Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer mortality. While significant advancements have been made in its treatment and management, it remains incurable due to tumor recurrence. The molecular mechanisms driving NSCLC involving protein-coding genes have been extensively studied. However, systematically identifying and characterizing the regulatory factors involved in NSCLC can also provide invaluable insight into the pathways involved and aid in developing novel therapeutic and diagnostic strategies. Long non-coding RNAs (lncRNAs) are a class of non-coding r

Not only 'in theory', but it is used for ancestry testing. Coding DNA (exonic regions) tend to be more highly conserved between individuals, as changes to the sequence are more likely to have a deleterious effect on an important phenotype (think a mutation which makes someone only have a single arm). Non-coding DNA is less constrained by selection and varies more between individuals / ethnic groups. This makes it more useful for identifying variants specific to different ethnicities, which makes the basis of ancestry testing. Typically in ancestry testing SNPs which show evidence of being under some kind of functional selection (i.e. are out of Hardy-Weinberg equilibrium) are excluded from the analysis. Neutrally evolving SNPs (which are more likely to be found in non-coding regions) are more likely to reflect the true population phylogeny. I'll try and update this post with some referen

of evolutionary paradigms for a long time to come, and will play a unique role in linking … expand its habitat by invading coding as well as non-coding DNA, without necessarily killing … argued, the overall amount of DNA plays a key role in determining nuclear volume (Cavalier-Smith