Project description:Here we reveal a lncRNA-transcription factor network with the MAF/MAFB transcription factors as central players in directing the epidermal differentiation program.
Project description:Using kinetic gene expression analysis of regenerated epidermis over a 7 day time-course, we identify a lncRNA-transription factor network with the MAF/MAFB transcription factors as central players in directing the epidermal differentiation program.
Project description:MafB is a member of the Maf family of bZip transcription factor and plays important roles in the developmental processes of various tissues, as well as in cell-type specific gene expression. MafB is expressed in differentiating keratinocytes in mice and is transcriptionally up-regulated upon human keratinocyte differentiation in vitro. In MafB-deficient mice, epidermal differentiation is partially impaired and the cornified layer is thinner. To gain insights into more detailed molecular mechanisms of MafB regulation of epidermal development, we performed microarray analysis of mRNAs isolated from dorsal skin epidermis of MafB-/- and wild-type mice at E18.5. Epidermis was separated from dorsal skin tissues of E18.5 mouse embryos (MafB-/- and WT) by Dispase (Life Technologies) treatment. Total RNA was isolated using Trizol reagent (Life Technologies), purified using an RNeasy mini kit (Qiagen), and subjected to microarray analysis.
Project description:MafB is a member of the Maf family of bZip transcription factor and plays important roles in the developmental processes of various tissues, as well as in cell-type specific gene expression. MafB is expressed in differentiating keratinocytes in mice and is transcriptionally up-regulated upon human keratinocyte differentiation in vitro. In MafB-deficient mice, epidermal differentiation is partially impaired and the cornified layer is thinner. To gain insights into more detailed molecular mechanisms of MafB regulation of epidermal development, we performed microarray analysis of mRNAs isolated from dorsal skin epidermis of MafB-/- and wild-type mice at E18.5.
Project description:Morphogenesis of the gonad requires cell-cell adhesion changes between diverse cell types. In the Drosophila gonad, the gene traffic jam regulates cell adhesion changes required for gonad formation and germ cell development (Li et al., 2003. Nature Cell Biol). To determine if the mammalian homologs of traffic jam in mammals, c-Maf and Mafb, also play a role in the transcription regulation of cell adhesion molecules in the mouse gonad, we performed a microarray analysis of FACS-purified Mafb-GFP-positive cells in E12.5 male control and c-Maf/Mafb mutant gonads. We used microarrays to determine genes affected by c-Maf mutation in E12.5 mouse gonad/mesonephros interstitial cells and macrophages E12.5 XY control (c-Maf+/-;Mafb-GFP+/-) and c-mutant (c-Maf-/-;Mafb-GFP+/-) gonad/interstitial interstitial cells and macrophages were obtained by FACS sorting of Mafb-GFP-positive cells. RNA was extracted for subsequent hybridization on Affymetrix microarrays.
Project description:Morphogenesis of the gonad requires cell-cell adhesion changes between diverse cell types. In the Drosophila gonad, the gene traffic jam regulates cell adhesion changes required for gonad formation and germ cell development (Li et al., 2003. Nature Cell Biol). To determine if the mammalian homologs of traffic jam in mammals, c-Maf and Mafb, also play a role in the transcription regulation of cell adhesion molecules in the mouse gonad, we performed a microarray analysis of FACS-purified Mafb-GFP-positive cells in E12.5 male control and c-Maf/Mafb mutant gonads. We used microarrays to determine genes affected by c-Maf mutation in E12.5 mouse gonad/mesonephros interstitial cells and macrophages
Project description:Numerous long non-coding RNAs (lncRNAs) were shown to have functional impact on cellular processes, such as human epidermal homeostasis, but for only a few the mode of action has been elucidated. Here, we report that lncRNA LINC00941 controls keratinocyte differentiation on a global level through association with the MTA2/NuRD complex, one of the major chromatin remodelers in cells. LINC00941 was found to interact with NuRD-associated MTA2, suppressing the expression of the transcription factor EGR3, a regulator of epidermal differentiation. Both LINC00941 and the MTA2/NuRD complex are enriched in non-differentiated keratinocytes and repress the expression of differentiation genes through epigenetic silencing of EGR3, consequentially preventing premature differentiation of human progenitor cells.
Project description:Differentiated macrophages can self-renew in tissues and expand long-term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network controlling self-renewal. Single cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells.