High-resolution 3D chromatin contact maps on CREST knock-out mouse motor neurons
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE281024 | GEO | 2026/08/20
REPOSITORIES: GEO
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Project description:High-resolution 3D chromatin contact maps on CREST knock-out mouse motor neurons
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Project description:Neuronal cell identity is partially established by epigenetic regulatory proteins, including chromatin remodeling complexes, which use their ATPase to modulate the accessibility of cis-regulatory DNA elements such as enhancers. Neuron-specific BAF (Brg1/Brm-associated factor) chromatin remodeling complexes contain a non-catalytic subunit, CREST, whose de novo mutations have been identified in motor neuron disease patients. However, the mechanisms by which CREST regulates neuronal gene expression programs during motor neuron differentiation remain unclear. Here, we elucidate the genome-wide mechanisms by which CREST regulates motor neuron differentiation from mouse embryonic stem cells. We found that CREST recognizes enhancers bound by motor neuron-specific transcription factors Onecut1 and Ngn2. Then, CREST selectively recruits the CBP histone acetyltransferase to acetylate histone H3 lysine 27 at neuronal enhancers, leading to the epigenetic activation of mature neuronal genes through long-range chromatin interactions. We also show that CREST-bound enhancers gain accessibility through selective recruitment of the neuron-specific Brm ATPase during the transition from neural progenitors to mature motor neurons. Furthermore, CREST knockout disrupts the expression of other subunits of neuronal BAF chromatin remodeling complexes, suggesting that CREST may influence the assembly of these complexes. Our findings reveal a non-canonical role of neuron-specific chromatin remodeling factors, demonstrating that CREST mediates communication between epigenetic regulators and neuron-specific enhancers, which are essential for proper neuronal function.
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Project description:Neuronal cell identity is partially established by epigenetic regulatory proteins, including chromatin remodeling complexes, which use their ATPase to modulate the accessibility of cis-regulatory DNA elements such as enhancers. Neuron-specific BAF (Brg1/Brm-associated factor) chromatin remodeling complexes contain a non-catalytic subunit, CREST, whose de novo mutations have been identified in motor neuron disease patients. However, the mechanisms by which CREST regulates neuronal gene expression programs during motor neuron differentiation remain unclear. Here, we elucidate the genome-wide mechanisms by which CREST regulates motor neuron differentiation from mouse embryonic stem cells. We found that CREST recognizes enhancers bound by motor neuron-specific transcription factors Onecut1 and Ngn2. Then, CREST selectively recruits the CBP histone acetyltransferase to acetylate histone H3 lysine 27 at neuronal enhancers, leading to the epigenetic activation of mature neuronal genes through long-range chromatin interactions. We also show that CREST-bound enhancers gain accessibility through selective recruitment of the neuron-specific Brm ATPase during the transition from neural progenitors to mature motor neurons. Furthermore, CREST knockout disrupts the expression of other subunits of neuronal BAF chromatin remodeling complexes, suggesting that CREST may influence the assembly of these complexes. Our findings reveal a non-canonical role of neuron-specific chromatin remodeling factors, demonstrating that CREST mediates communication between epigenetic regulators and neuron-specific enhancers, which are essential for proper neuronal function.
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Project description:The cranial neural crest cells are pluripotent cells that provide head skeletogenic mesenchyme and are crucial for craniofacial patterning. Here, we analyzed the in vivo chromatin landscapes of mouse cranial neural crest subpopulations. Early postmigratory neural crest subpopulations contributing to distinct mouse craniofacial structures displayed similar chromatin accessibility patterns, yet differed transcriptionally. Accessible promoters and enhancers of differentially silenced genes carried H3K27me3/H3K4me2 bivalent chromatin marks embedded in large Ezh2-dependent Polycomb domains, indicating transcriptional poising. These postmigratory bivalent regions were already present in neural crest premigratory progenitors. At Polycomb domains, H3K27me3 antagonized H3K4me2 deposition, which was restricted to accessible sites. Thus, bivalent Polycomb domains provide a chromatin template for the regulation of cranial neural crest cell positional identity in vivo contributing novel insights into the epigenetic regulation of face morphogenesis.
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Project description:The cranial neural crest cells are pluripotent cells that provide head skeletogenic mesenchyme and are crucial for craniofacial patterning. Here, we analyzed the in vivo chromatin landscapes of mouse cranial neural crest subpopulations. Early postmigratory neural crest subpopulations contributing to distinct mouse craniofacial structures displayed similar chromatin accessibility patterns, yet differed transcriptionally. Accessible promoters and enhancers of differentially silenced genes carried H3K27me3/H3K4me2 bivalent chromatin marks embedded in large Ezh2-dependent Polycomb domains, indicating transcriptional poising. These postmigratory bivalent regions were already present in neural crest premigratory progenitors. At Polycomb domains, H3K27me3 antagonized H3K4me2 deposition, which was restricted to accessible sites. Thus, bivalent Polycomb domains provide a chromatin template for the regulation of cranial neural crest cell positional identity in vivo contributing novel insights into the epigenetic regulation of face morphogenesis.
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Project description:The cranial neural crest cells are pluripotent cells that provide head skeletogenic mesenchyme and are crucial for craniofacial patterning. Here, we analyzed the in vivo chromatin landscapes of mouse cranial neural crest subpopulations. Early postmigratory neural crest subpopulations contributing to distinct mouse craniofacial structures displayed similar chromatin accessibility patterns, yet differed transcriptionally. Accessible promoters and enhancers of differentially silenced genes carried H3K27me3/H3K4me2 bivalent chromatin marks embedded in large Ezh2-dependent Polycomb domains, indicating transcriptional poising. These postmigratory bivalent regions were already present in neural crest premigratory progenitors. At Polycomb domains, H3K27me3 antagonized H3K4me2 deposition, which was restricted to accessible sites. Thus, bivalent Polycomb domains provide a chromatin template for the regulation of cranial neural crest cell positional identity in vivo contributing novel insights into the epigenetic regulation of face morphogenesis.
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