scholarly journals Nap1l2 Promotes Histone Acetylation Activity during Neuronal Differentiation

2007 ◽  
Vol 27 (17) ◽  
pp. 6093-6102 ◽  
Author(s):  
Mikaël Attia ◽  
Christophe Rachez ◽  
Antoine De Pauw ◽  
Philip Avner ◽  
Ute Christine Rogner
Keyword(s):  
Histone Acetylation ◽  
Neuronal Differentiation ◽  
Nucleosome Assembly ◽  
Cell Type ◽  
Cell Stage ◽  
Transcriptional Changes ◽  
Cell Type Specific ◽  
Mediate Cell ◽  
Developing Neurons ◽  
Assembly Proteins

ABSTRACT The deletion of the neuronal Nap1l2 (nucleosome assembly protein 1-like 2) gene in mice causes neural tube defects. We demonstrate here that this phenotype correlates with deficiencies in differentiation and increased maintenance of the neural stem cell stage. Nap1l2 associates with chromatin and interacts with histones H3 and H4. Loss of Nap1l2 results in decreased histone acetylation activity, leading to transcriptional changes in differentiating neurons, which include the marked downregulation of the Cdkn1c (cyclin-dependent kinase inhibitor 1c) gene. Cdkn1c expression normally increases during neuronal differentiation, and this correlates with the specific recruitment of the Nap1l2 protein and an increase in acetylated histone H3K9/14 at the site of Cdkn1c transcription. These results lead us to suggest that the Nap1l2 protein plays an important role in regulating transcription in developing neurons via the control of histone acetylation. Our data support the idea that neuronal nucleosome assembly proteins mediate cell-type-specific mechanisms of establishment/modification of a chromatin-permissive state that can affect neurogenesis and neuronal survival.

scholarly journals Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation

2008 ◽  
Vol 105 (45) ◽  
pp. 17414-17419 ◽  
Author(s):  
A. Y. Choo ◽  
S.-O. Yoon ◽  
S. G. Kim ◽  
P. P. Roux ◽  
J. Blenis
Keyword(s):  
Mrna Translation ◽  
Cell Type ◽  
Cell Type Specific ◽  
Mediate Cell

scholarly journals Single-nucleus RNA-seq reveals dysregulation of striatal cell identity due to Huntington’s disease mutations

2020 ◽  
Author(s):  
Sonia Malaiya ◽  
Marcia Cortes-Gutierrez ◽  
Brian R. Herb ◽  
Sydney R. Coffey ◽  
Samuel R.W. Legg ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Cell Types ◽  
Transcriptional Networks ◽  
Rna Seq ◽  
Cell Type ◽  
Cell Identity ◽  
Transcriptional Changes ◽  
Cell Type Specific

ABSTRACTHuntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by a trinucleotide expansion in exon 1 of the huntingtin (Htt) gene. Cell death in HD occurs primarily in striatal medium spiny neurons (MSNs), but the involvement of specific MSN subtypes and of other striatal cell types remains poorly understood. To gain insight into cell type-specific disease processes, we studied the nuclear transcriptomes of 4,524 cells from the striatum of a genetically precise knock-in mouse model of the HD mutation, HttQ175/+, and from wildtype controls. We used 14-15-month-old mice, a time point roughly equivalent to an early stage of symptomatic human disease. Cell type distributions indicated selective loss of D2 MSNs and increased microglia in aged HttQ175/+ mice. Thousands of differentially expressed genes were distributed across most striatal cell types, including transcriptional changes in glial populations that are not apparent from RNA-seq of bulk tissue. Reconstruction of cell typespecific transcriptional networks revealed a striking pattern of bidirectional dysregulation for many cell type-specific genes. Typically, these genes were repressed in their primary cell type, yet de-repressed in other striatal cell types. Integration with existing epigenomic and transcriptomic data suggest that partial loss-of-function of the Polycomb Repressive Complex 2 (PRC2) may underlie many of these transcriptional changes, leading to deficits in the maintenance of cell identity across virtually all cell types in the adult striatum.

scholarly journals Spatiotemporal dynamics of SETD5-containing NCoR–HDAC3 complex determines enhancer activation for adipogenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yoshihiro Matsumura ◽  
Ryo Ito ◽  
Ayumu Yajima ◽  
Rei Yamaguchi ◽  
Toshiya Tanaka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Acetylation ◽  
Ubiquitin Ligase ◽  
Cellular Differentiation ◽  
Specific Gene ◽  
Cell Type ◽  
Set Domain ◽  
Protein Levels ◽  
Primed State ◽  
Cell Type Specific

AbstractEnhancer activation is essential for cell-type specific gene expression during cellular differentiation, however, how enhancers transition from a hypoacetylated “primed” state to a hyperacetylated-active state is incompletely understood. Here, we show SET domain-containing 5 (SETD5) forms a complex with NCoR-HDAC3 co-repressor that prevents histone acetylation of enhancers for two master adipogenic regulatory genes Cebpa and Pparg early during adipogenesis. The loss of SETD5 from the complex is followed by enhancer hyperacetylation. SETD5 protein levels were transiently increased and rapidly degraded prior to enhancer activation providing a mechanism for the loss of SETD5 during the transition. We show that induction of the CDC20 co-activator of the ubiquitin ligase leads to APC/C mediated degradation of SETD5 during the transition and this operates as a molecular switch that facilitates adipogenesis.

scholarly journals CHAS, a deconvolution tool, infers cell type-specific signatures in bulk brain histone acetylation studies of brain disorders

2021 ◽  
Author(s):  
Kitty B Murphy ◽  
Alexi Nott ◽  
Sarah J Marzi
Keyword(s):  
Histone Acetylation ◽  
Brain Tissue ◽  
Association Studies ◽  
Regulatory Elements ◽  
Autism Spectrum ◽  
Epigenetic Mark ◽  
Brain Disorders ◽  
Cell Type ◽  
Brain Disorder ◽  
Cell Type Specific

Chromatin profiling studies have shown the importance of gene regulation in driving heritability and environmental risk of brain disorders. Acetylation of histone H3 lysine 27 (H3K27ac) has emerged as an informative disease-associated epigenetic mark. However, cell type-specific contributions to epigenetic dysregulation in disease are unclear as studies have often used bulk brain tissue. Therefore, methods for the deconvolution of bulk H3K27ac profiles are critical. Here we developed the Cell type-specific Histone Acetylation Score (CHAS), a computational tool for inferring cell type-specific signatures in bulk brain H3K27ac profiles. CHAS annotates peaks identified in bulk brain studies of H3K27ac to cell type-specific signals in four major brain cell types, and derives cell type-specific histone acetylation scores as a proxy for cell type proportion. Our method was validated in pseudo-bulk samples and applied to three brain disorder epigenome-wide association studies conducted on bulk brain tissue. CHAS exposed shifts in cellular proportions in Alzheimer's disease (AD), in line with neuropathology, and identified disrupted gene regulatory elements in oligodendrocytes in AD and microglia in autism spectrum disorder (ASD). This contrasts with heritability-based enrichment analyses which indicate genetic risk is associated with microglia in AD and neurons in ASD. Our approach identified cell type specific signalling pathways and putative upstream transcription factors associated with these elements. CHAS enables deconvolution of H3K27ac in bulk brain tissue, yielding cell type-specific biological insights into brain disease-associated regulatory variation.

scholarly journals High Glutathione and Glutathione Peroxidase-2 Levels Mediate Cell-Type-Specific DNA Damage Protection in Human Induced Pluripotent Stem Cells

2015 ◽  
Vol 4 (5) ◽  
pp. 886-898 ◽  
Author(s):  
Benjamin Dannenmann ◽  
Simon Lehle ◽  
Dominic G. Hildebrand ◽  
Ayline Kübler ◽  
Paula Grondona ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Glutathione Peroxidase ◽  
Pluripotent Stem Cells ◽  
Cell Type ◽  
Cell Type Specific ◽  
Mediate Cell ◽  
Induced Pluripotent ◽  
Dna Damage Protection ◽  
Damage Protection

scholarly journals Cell type specific gene expression profiling reveals a role for complement component C3 in neutrophil responses to tissue damage

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ruth A. Houseright ◽  
Emily E. Rosowski ◽  
Pui-Ying Lam ◽  
Sebastien J. M. Tauzin ◽  
Oscar Mulvaney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tissue Damage ◽  
Bacterial Infections ◽  
Affinity Purification ◽  
Specific Gene ◽  
Cell Type ◽  
Zebrafish Larvae ◽  
Complement Component C3 ◽  
Transcriptional Changes ◽  
Cell Type Specific

Abstract Tissue damage induces rapid recruitment of leukocytes and changes in the transcriptional landscape that influence wound healing. However, the cell-type specific transcriptional changes that influence leukocyte function and tissue repair have not been well characterized. Here, we employed translating ribosome affinity purification (TRAP) and RNA sequencing, TRAP-seq, in larval zebrafish to identify genes differentially expressed in neutrophils, macrophages, and epithelial cells in response to wounding. We identified the complement pathway and c3a.1, homologous to the C3 component of human complement, as significantly increased in neutrophils in response to wounds. c3a.1−/− zebrafish larvae have impaired neutrophil directed migration to tail wounds with an initial lag in recruitment early after wounding. Moreover, c3a.1−/− zebrafish larvae have impaired recruitment to localized bacterial infections and reduced survival that is, at least in part, neutrophil mediated. Together, our findings support the power of TRAP-seq to identify cell type specific changes in gene expression that influence neutrophil behavior in response to tissue damage.

scholarly journals Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Brittany P. Todd ◽  
Michael S. Chimenti ◽  
Zili Luo ◽  
Polly J. Ferguson ◽  
Alexander G. Bassuk ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Type I Interferon ◽  
Transcriptional Response ◽  
Type I ◽  
Cell Type ◽  
Specific Analysis ◽  
Transcriptional Changes ◽  
Severe Tbi ◽  
Cell Type Specific ◽  
Glial Reactivity

Abstract Background Traumatic brain injury (TBI) is a leading cause of death and disability that lacks neuroprotective therapies. Following a TBI, secondary injury response pathways are activated and contribute to ongoing neurodegeneration. Microglia and astrocytes are critical neuroimmune modulators with early and persistent reactivity following a TBI. Although histologic glial reactivity is well established, a precise understanding of microglia and astrocyte function following trauma remains unknown. Methods Adult male C57BL/6J mice underwent either fluid percussion or sham injury. RNA sequencing of concurrently isolated microglia and astrocytes was conducted 7 days post-injury to evaluate cell-type-specific transcriptional responses to TBI. Dual in situ hybridization and immunofluorescence were used to validate the TBI-induced gene expression changes in microglia and astrocytes and to identify spatial orientation of cells expressing these genes. Comparative analysis was performed between our glial transcriptomes and those from prior reports in mild TBI and other neurologic diseases to determine if severe TBI induces unique states of microglial and astrocyte activation. Results Our findings revealed sustained, lineage-specific transcriptional changes in both microglia and astrocytes, with microglia showing a greater transcriptional response than astrocytes at this subacute time point. Microglia and astrocytes showed overlapping enrichment for genes related to type I interferon signaling and MHC class I antigen presentation. The microglia and astrocyte transcriptional response to severe TBI was distinct from prior reports in mild TBI and other neurodegenerative and neuroinflammatory diseases. Conclusion Concurrent lineage-specific analysis revealed novel TBI-specific transcriptional changes; these findings highlight the importance of cell-type-specific analysis of glial reactivity following TBI and may assist with the identification of novel, targeted therapies.

scholarly journals Cell type-specific transcriptional programs in mouse prefrontal cortex during adolescence and addiction

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aritra Bhattacherjee ◽  
Mohamed Nadhir Djekidel ◽  
Renchao Chen ◽  
Wenqiang Chen ◽  
Luis M. Tuesta ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Cell Type ◽  
Cognitive Behaviors ◽  
Disease States ◽  
Transcriptional Dynamics ◽  
Chronic Cocaine ◽  
Transcriptional Changes ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Unique Cell

Abstract Coordinated activity-induced transcriptional changes across multiple neuron subtypes of the prefrontal cortex (PFC) play a pivotal role in encoding and regulating major cognitive behaviors. Yet, the specific transcriptional programs in each neuron subtype remain unknown. Using single-cell RNA sequencing (scRNA-seq), here we comprehensively classify all unique cell subtypes in the PFC. We analyze transcriptional dynamics of each cell subtype under a naturally adaptive and an induced condition. Adaptive changes during adolescence (between P21 and P60), a highly dynamic phase of postnatal neuroplasticity, profoundly impacted transcription in each neuron subtype, including cell type-specific regulation of genes implicated in major neuropsychiatric disorders. On the other hand, an induced plasticity evoked by chronic cocaine addiction resulted in progressive transcriptional changes in multiple neuron subtypes and became most pronounced upon prolonged drug withdrawal. Our findings lay a foundation for understanding cell type-specific postnatal transcriptional dynamics under normal PFC function and in neuropsychiatric disease states.

Nucleosome assembly proteins and their interacting proteins in neuronal differentiation

2013 ◽  
Vol 534 (1-2) ◽  
pp. 20-26 ◽  
Author(s):  
Mikaël Attia ◽  
Christophe Rachez ◽  
Philip Avner ◽  
Ute Christine Rogner
Keyword(s):  
Neuronal Differentiation ◽  
Interacting Proteins ◽  
Nucleosome Assembly ◽  
Assembly Proteins
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