1,720,993 research outputs found
Roles of chromatin remodeling BAF complex in neural differentiation and reprogramming
No full textATP-dependent BAF chromatin remodeling complexes play an essential role in the maintenance of the gene expression program by regulating the structure of chromatin. There is increasing evidence that BAF complexes based on the alternative ATPase subunits, Brg1 and Brm, control the differentiation of neural stem cells (NSCs) to generate distinct neural cell types and modulate trans-differentiation between cell types. The BAF complexes have dedicated functions at different stages of neural differentiation that appear to arise by combinatorial assembly of their subunits. Furthermore, the differentiation of NSCs is regulated by the tight interactions between the BAF chromatin remodeling complex and the transcriptional machinery. Here, we review recent insights into the functional interaction between BAF complexes and various transcription factors (TFs) in neural differentiation and cellular reprogramming.University Medicine Gottingen (UMG); DFG [TU432/1-1
Chromatin Remodeling BAF (SWI/SNF) Complexes in Neural Development and Disorders
Full text linkThe ATP-dependent BRG1/BRM associated factor (BAF) chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra's syndrome spectrum, Hirschsprung's disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders
BAF chromatin remodeling complex: Cortical size regulation and beyond.
No full textThe multi-subunit chromatin remodeling BAF complex controls different developmental processes. Using cortex-specific conditional knockout and overexpression mouse models, we have recently reported that BAF170, a subunit of the vertebrate BAF chromatin remodeling complex, interacts with transcription factor (TF) Pax6 to control cortical size and volume. The mechanistic basis includes suppression of the expression of Pax6 target genes, which are required for genesis of cortical intermediate progenitors (IPs) and specification of late neuronal subtype identity. In addition, we showed that a dynamic competition between BAF170 and BAF155 subunits within the BAF complex during progression of neurogenesis is a primary event in modulating the size of the mammalian cortex. Here, we present additional insights into the interaction between the BAF complex and TF Pax6 in the genesis of IPs of the developing cortex. Furthermore, we show that such competition between BAF170 and BAF155 is involved as well in the determination of the size of the embryonic body. Our results add new insights into a cell-intrinsic mechanism, mediated by the chromatin remodeling BAF complex that controls vertebrate body shape and size
Control of cerebral size and thickness
No full textThe mammalian neocortex is a sheet of cells covering the cerebrum that provides the structural basis for the perception of sensory inputs, motor output responses, cognitive function, and mental capacity of primates. Recent discoveries promote the concept that increased cortical surface size and thickness in phylogenetically advanced species is a result of an increased generation of neurons, a process that underlies higher cognitive and intellectual performance in higher primates and humans. Here, we review some of the advances in the field, focusing on the diversity of neocortical progenitors in different species and the cellular mechanisms of neurogenesis. We discuss recent views on intrinsic and extrinsic molecular determinants, including the role of epigenetic chromatin modifiers and microRNA, in the control of neuronal output in developing cortex and in the establishment of normal cortical architecture
Postnatal Cranial Characterization in a Mouse Model of Cortex‐Specific Overexpression of BAF170
No full textNational Institutes of Health https://doi.org/10.13039/100000002National Institute of Dental and Craniofacial Research https://doi.org/10.13039/100000072National Institutes of Health https://doi.org/10.13039/10000000
Intranuclear immunostaining-based FACS protocol from embryonic cortical tissue
No full textCell sorting can be used to purify cell populations for cell type-specific molecular probing. Fluorescence-activated cell sorting (FACS) coupled with high-throughput sequencing affords molecular signature identification for specific cell types. FACS has many challenges that limit comprehensive cell purification from the brain, leading to incomplete molecular characterization. Here, we present the intranuclear immunostaining-based FACS protocol with several modified steps, which allows optimized nuclei/cell sorting from mouse or human embryonic cortical tissue for distinct downstream molecular investigation of basal intermediate progenitors
ATP-Dependent Chromatin Remodeling During Cortical Neurogenesis
No full textThe generation of individual neurons (neurogenesis) during cortical development occurs in discrete steps that are subtly regulated and orchestrated to ensure normal histogenesis and function of the cortex. Notably, various gene expression programs are known to critically drive many facets of neurogenesis with a high level of specificity during brain development. Typically, precise regulation of gene expression patterns ensures that key events like proliferation and differentiation of neural progenitors, specification of neuronal subtypes, as well as migration and maturation of neurons in the developing cortex occur properly. ATP-dependent chromatin remodeling complexes regulate gene expression through utilization of energy fromATP hydrolysis to reorganize chromatin structure. These chromatin remodeling complexes are characteristically multimeric, with some capable of adopting functionally distinct conformations via subunit reconstitution to perform specific roles in major aspects of cortical neurogenesis. In this review, we highlight the functions of such chromatin remodelers during cortical development. We also bring together various proposed mechanisms by which ATP-dependent chromatin remodelers function individually or in concert, to specifically modulate vital steps in cortical neurogenesis
RBM15 Modulates the Function of Chromatin Remodeling Factor BAF155 Through RNA Methylation in Developing Cortex
No full textMapping of domain-mediated protein-protein interaction by SPOT peptide assay
No full textSummary: Identification of peptides mediating protein-protein interaction (PPI) is crucial for understanding the function of interlinked proteins in cellular processes and amino acid-associated diseases. Traditional PPI assays are laborious, involving the generation of many truncated proteins. SPOT peptide assay allows high-throughput detection of domains essential for PPI by synthesizing several hundred peptides on a cellulose membrane. Here, we present a rapid SPOT peptide protocol for identifying the binding motifs, which mediate interaction between the chromatin remodeling factors BAF155/BAF170 and the epigenetic factor Kdm6b.For complete details on the use and execution of this protocol, please refer to Narayanan et al. (2015)
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