Dermatology epigenetics

The processes of epidermal development in mammals are regulated by complex molecular mechanisms, such as histone modifications. Histone H3 lysine K4 (H3K4) methylation mediated by COMPASS methyltransferase is associated with gene activation, but its effect on epidermal lineage development remains unclear. Therefore, we constructed a mouse model of specific ASH2L (COMPASS methyltransferase core subunit) deletion in epidermal progenitor cells and investigated its effect on the development of mouse epidermal lineage...

BACKGROUND: Treg plays a pivotal role in the suppression of Th2 cell and the maintenance of immune homeostasis. The precise molecular mechanism underlying the disruption of Treg suppression of Th2 cell and the promotion of Th2 type inflammation in allergic diseases remains elusive. OBJECTIVE: This study aims to investigate the molecular mechanism underlying quantitative and functional changes of Treg in AD. METHODS: The molecular mechanism was investigated using flow cytometry, mRNA sequencing, co-culture experiments, co-immunoprecipitation, chromatin immunoprecipitation, and bisulfite sequencing in vitro or in AD mice model and patients with AD...

Keratinocytes, the principal epidermal cells, play a vital role in maintaining the structural integrity and functionality of the skin. Beyond their protective role, keratinocytes are key contributors to the process of wound healing, as they migrate to injury sites, proliferate, and generate new layers of epidermis, facilitating tissue repair and remodeling. Moreover, keratinocytes actively participate in the skin's immune responses, expressing pattern recognition receptors (PRRs) to detect microbial components and interact with immune cells to influence adaptive immunity...

No abstract text is available yet for this article.

BACKGROUND: TET2 participates in tumor progression and intrinsic immune homeostasis via epigenetic regulation. TET2 has been reported to be involved in maintaining epithelial barrier homeostasis and inflammation. Abnormal epidermal barrier function and TET2 expression have been detected in psoriatic lesions. However, the mechanisms underlying the role of TET2 in psoriasis have not yet been elucidated. OBJECTIVE: To define the role of TET2 in maintaining epithelial barrier homeostasis and the exact epigenetic mechanism in the dysfunction of the epidermal barrier in psoriasis...

Dedifferentiation or phenotype switching refers to the transition from a proliferative to an invasive cellular state. We previously identified a 122-gene epigenetic gene signature that classifies primary melanomas as low- versus high-risk (denoted as Epgn1 or Epgn3). We found that the transcriptomes of the Epgn1 low-risk and Epgn3 high-risk cells are similar to the proliferative and invasive cellular states, respectively. These signatures were further validated in melanoma tumor samples. Examination of the chromatin landscape revealed differential H3K27 acetylation in the Epgn1 low-risk versus Epgn3 high-risk cell lines that corroborated with a differential super-enhancer and enhancer landscape...

Virtually all patients with BRAF-mutant melanoma develop resistance to MAPK inhibitors largely through non-mutational events. Although the epigenetic landscape is shown to be altered in therapy-resistant melanomas and other cancers, a specific targetable epigenetic mechanism has not been validated to date. Here, we evaluate the CoREST repressor complex and the recently developed bivalent inhibitor, corin, within the context of melanoma phenotype plasticity and therapeutic resistance. We find that CoREST is a critical mediator of the major distinct melanoma phenotypes and that corin treatment of melanoma cells leads to phenotype reprogramming...

The evolutionary establishment of an internal biological clock is a primordial event tightly associated with a 24-h period. Changes in the circadian rhythm can affect cellular functions, including proliferation, DNA repair and redox state. Even isolated organs, tissues and cells can maintain an autonomous circadian rhythm. These cell-autonomous molecular mechanisms are driven by intracellular clock genes, such as BMAL1. Little is known about the role of core clock genes and epigenetic modifications in the skin...

Lymphomas of the eye and ocular adnexa are rare lymphoproliferative diseases of the ocular and ocular adnexal tissue. The incidence of these diseases has been rapidly increasing over the past few decades. The exact pathogenesis remains unknown, but it is postulated to be multifactorial and includes genetic aberrations, epigenetic and environmental factors, infectious agents, and chronic antigenic stimulation. The majority of ocular and ocular adnexal lymphomas are of B-cell origin; except for eyelid lymphomas, which are more often of T cell type...

Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin disorder, which typically occurs during puberty or early adulthood. The pathogenesis of HS is complex and multifactorial; a close interaction between hormonal, genetic, epigenetics factors, host-specific aspects, and environmental influences contributes to the susceptibility, onset, severity, and clinical course of this disease, although the exact molecular mechanisms are still being explored. Epigenetics is currently emerging as an interesting field of investigation that could potentially shed light on the molecular intricacies underlying HS, but there is much still to uncover on the subject...

Patients with a history of endometriosis have an increased risk of developing various autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis and celiac disease. There is a potential association between endometriosis and an increased susceptibility for Sjögren's syndrome (SS). SS is a common chronic, inflammatory, systemic, autoimmune, multifactorial disease of complex pathology, with genetic, epigenetic and environmental factors contributing to the development of this condition...

No abstract text is available yet for this article.

Autoimmune connective tissue disorders, including systemic lupus erythematosus, systemic sclerosis (SSc) and dermatomyositis (DM), often manifest with debilitating cutaneous lesions and can result in systemic organ damage that may be life-threatening. Despite recent therapeutic advancements, many patients still experience low rates of sustained remission and significant treatment toxicity. While genetic predisposition plays a role in these connective tissue disorders, the relatively low concordance rates among monozygotic twins (ranging from approximately 4% for SSc to about 11%-50% for SLE) have prompted increased scrutiny of the epigenetic factors contributing to these diseases...

BACKGROUND: Healing of diabetic wounds, characterized by impaired angiogenesis, remains a clinical challenge. E3 ligase have been identified as potential therapeutic targets of wound healing. OBJECTIVE: We assessed the role of E3 ligase NEDD4 in the context of angiogenesis and diabetic wound healing. METHODS: The mRNA expression levels of NEDD4, TSP1 and VEGF were determined by real-time PCR. Western blotting was used to evaluate the protein expression of NEDD4, TSP1 and VEGF...

Basal cell carcinoma (BCC) is the most common malignant tumour arising from the basal cells of the epidermis or follicular structures. The aetiology of BCC is a multifactorial combination of genotype, phenotype and environmental factors. The pathogenesis of BCC remains unclear, with diverse and complex signalling pathways involved. ARHGAP40 is a Rho GTPase-activating protein (RhoGAP). Rho GTPases play a crucial role in the formation and progression of numerous cancers. The expression levels and roles of ARHGAP40 in BCC have not been explored...

The development of cutaneous melanoma of the skin based on dysplastic nevus is not uncommon. The causes of the progression of nevi to melanomas are numerous and not well understood at present. Certain genetic and epigenetic factors have a major influence on this evolution. We describe a 46-year-old female patient with multiple dermal melanocytic nevi who developed a polypoid melanoma in one of them. After a carefully performed anamnesis, the mole that developed into melanoma was found to be localized in the dorsal area adjacent to the brassiere and underwent permanent and daily mechanical irradiation during the last 6-7 years...

RNA modification is considered as an epigenetic modification that plays an indispensable role in biological processes such as gene expression and genome editing without altering nucleotide sequence, but the molecular mechanism of RNA modification has not been discussed systematically in the development of skin diseases. This article mainly presents the whole picture of theoretical achievements on the potential role of RNA modification in dermatology. Furthermore, this article summarizes the latest advances in clinical practice related with RNA modification, including its detection methods and drug development...

Regulatory elements, particularly enhancers, play a crucial role in disease susceptibility and progression. Enhancers are DNA sequences that activate gene expression and can be affected by epigenetic modifications, interactions with transcription factors (TFs), or changes to the enhancer DNA sequence itself. Altered enhancer activity impacts gene expression and contributes to disease. In this review, we define enhancers and the experimental techniques used to identify and characterize them. We also discuss recent studies that examine how enhancers contribute to atopic dermatitis (AD) and psoriasis...

BACKGROUND: Primary cutaneous CD4+ small/medium-sized pleomorphic T-Cell lymphoproliferative disorder (PC-SMTLD) has been considered as a controversial dermatological disease that has been included in cutaneous T-cell lymphoma group, presenting most commonly as a solitary nodule and/or plaque with a specific and characteristic head and neck predilection. Due to the considerable overlap between PC-SMTLD and pseudolymphoma (PL), the differential diagnosis is often challenging. Methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas...

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a severe impact on patients' quality of life through its recurrent and painful nature, as well as its comorbidity burden. The shift in the pathogenic paradigm from a condition of the apocrine glands to an autoinflammatory disease associated with follicular destruction has rendered its understanding difficult, as there are still large gaps in pinpointing the underlying mechanisms, which cannot currently explain the existing clinical variation and as a result, translate into suboptimal therapy...