ABSTRACT
Myelinating Schwann cells in the vertebrate peripheral nervous system rely on Brg1 (Smarca4) for terminal differentiation. Brg1 serves as central ATP-hydrolyzing subunit of the chromatin remodelling BAF complexes and is recruited during myelination as part of these complexes by the transcription factor Sox10 in Schwann cells. Here, we analyzed the role of Brg1 during development of myelinating oligodendrocytes in the CNS of the mouse. Following Brg1 deletion in oligodendrocyte precursors, these cells showed normal survival, proliferation, and migration. A mild but significant reduction in the number of oligodendrocytes with myelin gene expression in the absence of Brg1 points to a contribution to oligodendroglial differentiation but also shows that the role of Brg1 is much less prominent than during Schwann cell differentiation. Additionally, we failed to obtain evidence for a genetic interaction between Brg1 and Sox10 comparable with the one in Schwann cells. This argues that similarities exist between the regulatory networks and mechanisms in both types of myelinating glia but that the exact mode of action and the relevance of functional interactions differ, pointing to a surprising degree of variability in the control of myelination.
Subject(s)
Cell Differentiation/physiology , Chromatin Assembly and Disassembly/physiology , DNA Helicases/deficiency , Nuclear Proteins/deficiency , Oligodendroglia/physiology , Transcription Factors/deficiency , Animals , Cells, Cultured , DNA Helicases/genetics , Female , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Transgenic , Nuclear Proteins/genetics , Transcription Factors/geneticsABSTRACT
Schwann cells produce myelin sheaths and thereby permit rapid saltatory conductance in the vertebrate peripheral nervous system. Their stepwise differentiation from neural crest cells is driven by a defined set of transcription factors. How this is linked to chromatin changes is not well understood. Here we show that the glial transcription factor Sox10 functions in Schwann cells by recruiting Brg1-containing chromatin-remodeling complexes via Baf60a to regulatory regions of Oct6 and Krox20 genes. It thereby stimulates expression of these transcriptional regulators that then cooperate with Sox10 to convert immature into myelinating Schwann cells. The functional interaction between Sox10 and Brg1 is evident from gain- and loss-of-function studies, similar neuropathies in the corresponding mouse mutants, and an aggravated neuropathy in compound mutants. Our results demonstrate that the transcription factor-mediated recruitment of the chromatin-remodeling machinery to specific genomic loci is an essential driving force for Schwann cell differentiation and myelination.
Subject(s)
Cell Differentiation/physiology , Chromatin Assembly and Disassembly/physiology , DNA Helicases/physiology , Myelin Sheath/physiology , Nuclear Proteins/physiology , Schwann Cells/cytology , Schwann Cells/metabolism , Transcription Factors/physiology , Animals , Cell Line, Tumor , Chick Embryo , Chickens , DNA Helicases/genetics , HEK293 Cells , Humans , Mice , Mice, Transgenic , Myelin Sheath/ultrastructure , Nuclear Proteins/genetics , SOXE Transcription Factors/genetics , SOXE Transcription Factors/metabolism , SOXE Transcription Factors/physiology , Transcription Factors/geneticsABSTRACT
The Triticeae tribe of the plant Poaceae family contains some of the most important cereal crop plants for nutrition of humans and livestock such as wheat and barley. Despite the agronomical relevance of plant immunity, knowledge on mechanisms of disease or resistance in Triticeae is limited. It is hardly understood what actually stops a microbial invader when restricted by the plant and in how far a susceptible host plant contributes to pathogenesis. Transcriptional reprogramming of the host plant may be involved in both immunity and disease. This paper gives an overview about recent analyses of global pathogenesis-related transcriptional patterns in response of Triticeae to biotrophic or non-biotrophic fungal pathogens and their toxins. It highlights enriched biological functions in association with successful plant defence or disease as well as experiments that successfully translated gene expression data into analysis of gene functions.
Subject(s)
Host-Pathogen Interactions/genetics , Plant Proteins/genetics , Poaceae/genetics , Poaceae/microbiology , Transcription, Genetic/genetics , Gene Expression Regulation, Plant/geneticsABSTRACT
BAX INHIBITOR-1 (BI-1) is one of the few proteins known to have cross-kingdom conserved functions in negative control of programmed cell death. Additionally, barley BI-1 (HvBI-1) suppresses defense responses and basal resistance to the powdery mildew fungus Blumeria graminis f. sp. hordei and enhances resistance to cell death-provoking fungi when overexpressed in barley. Downregulation of HvBI-1 by transient-induced gene silencing or virus-induced gene silencing limited susceptibility to B. graminis f. sp. hordei, suggesting that HvBI-1 is a susceptibility factor toward powdery mildew. Transient silencing of BI-1 did not limit supersusceptibility induced by overexpression of MLO. Transgenic barley plants harboring an HvBI-1 RNA interference (RNAi) construct displayed lower levels of HvBI-1 transcripts and were less susceptible to powdery mildew than wild-type plants. At the cellular level, HvBI-1 RNAi plants had enhanced resistance to penetration by B. graminis f. sp. hordei. These data support a function of BI-1 in modulating cell-wall-associated defense and in establishing full compatibility of B. graminis f. sp. hordei with barley.
