Project description:The goal of this study was to identify lncRNAs and novel transcripts that are differentially regulated in cutaneous squamous cell carcinoma (SCC) using RNA sequencing In this dataset, we include expression data from human skin tissue regenerated in the presence or absence of the putative lncRNA SMRT-2, which we have identified as a new regulator of differentiation.
Project description:Chromatin modifiers play critical roles in epidermal development, but the functions of histone deacetylases in this context are poorly understood. We find that the Class I HDAC, HDAC3, is expressed broadly in embryonic epidermis, and is required for its orderly stepwise stratification. Stability of HDAC3 protein in vivo is reliant on NCoR and SMRT, which function redundantly in epidermal development. However, point mutations in the NCoR and SMRT Deacetylase Activating Domains, which are required for HDAC3’s enzymatic function, permit normal stratification, indicating that HDAC3’s roles in this context are independent of its histone deacetylase activity. HDAC3 functions both in conjunction with, and independent of, KLF4 to repress premature expression of different sets of terminal differentiation genes and suppresses expression of inflammatory cytokines through a RelA-dependent mechanism. These data identify HDAC3 as a hub coordinating multiple aspects of epidermal barrier acquisition.
Project description:Chromatin modifiers play critical roles in epidermal development, but the functions of histone deacetylases in this context are poorly understood. We find that the Class I HDAC, HDAC3, is expressed broadly in embryonic epidermis, and is required for its orderly stepwise stratification. Stability of HDAC3 protein in vivo is reliant on NCoR and SMRT, which function redundantly in epidermal development. However, point mutations in the NCoR and SMRT Deacetylase Activating Domains, which are required for HDAC3’s enzymatic function, permit normal stratification, indicating that HDAC3’s roles in this context are independent of its histone deacetylase activity. HDAC3 functions both in conjunction with, and independent of, KLF4 to repress premature expression of different sets of terminal differentiation genes and suppresses expression of inflammatory cytokines through a RelA-dependent mechanism. These data identify HDAC3 as a hub coordinating multiple aspects of epidermal barrier acquisition. We used microarrays to determine transcriptional changes in Klf4 deleted epidermis compared to control.
Project description:Chromatin modifiers play critical roles in epidermal development, but the functions of histone deacetylases in this context are poorly understood. We find that the Class I HDAC, HDAC3, is expressed broadly in embryonic epidermis, and is required for its orderly stepwise stratification. Stability of HDAC3 protein in vivo is reliant on NCoR and SMRT, which function redundantly in epidermal development. However, point mutations in the NCoR and SMRT Deacetylase Activating Domains, which are required for HDAC3’s enzymatic function, permit normal stratification, indicating that HDAC3’s roles in this context are independent of its histone deacetylase activity. HDAC3 functions both in conjunction with, and independent of, KLF4 to repress premature expression of different sets of terminal differentiation genes and suppresses expression of inflammatory cytokines through a RelA-dependent mechanism. These data identify HDAC3 as a hub coordinating multiple aspects of epidermal barrier acquisition. We used microarrays to determine transcriptional changes in Hdac3 deleted epidermis compared to control and Ncor1/Ncor2 deleted epidermis compared to control.
Project description:Dynamic chemical modifications of RNA represent novel and fundamental mechanisms that regulate stemness and tissue homeostasis. Rejuvenation and wound repair of mammalian skin are sustained by epidermal progenitor cells, which are localized within the basal layer of the skin epidermis. N6-methyladenosine (m6A) is one of the most abundant modifications found in eukaryotic mRNA and lncRNA (long non-coding RNA). In this report, we survey changes of m6A RNA methylomes upon epidermal differentiation, and identify Pvt1, a lncRNA whose m6A modification is critically involved in sustaining stemness of epidermal progenitor cells. With genome-editing and a mouse genetics approach, we show that ablation of m6A methyltransferase or Pvt1 impairs the self-renewal and wound healing capability of skin. Mechanistically, methylation of Pvt1 transcripts enhances its interaction with MYC and stabilizes the MYC protein in epidermal progenitor cells. Our study presents a global view of epitranscriptomic dynamics that occur during epidermal differentiation and identifies the m6A modification of Pvt1 as a key signaling event involved in skin tissue homeostasis and wound repair.