Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA186929 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Epigenetic control of neural stem/progenitor cell fate is fundamental to achieve a fully brain architecture. Two intrinsic programs regulate neurogenesis, one by epigenetic-mediated gene transcription and another by cell cycle control. Whether and how these two are coordinated to determine temporally and spatially neural development remains unknown. Here we show that deletion of Trrap (Transcription translation associated protein), an essential cofactor for HAT (histone acetyltransferase), leads to severe brain atrophy due to a combination of cell death and a blockade of neuron production. Specifically, Trrap deletion forces differentiation of apical progenitor (AP) fate into basal progenitors (BP) and neurons thereby limiting the total neurogenic production. Despite TrrapM-bM-^@M-^Ys general role in transcriptional regulation, a genome-wide transcriptome analysis of neuroprogenitors identified the cell cycle regulators that are specifically affected by Trrap deletion. Furthermore, E2F-dependent recruitment of HAT and transcription factors to the promoter of cell cycle regulators is impaired in Trrap-deleted neuroprogenitors. Consistent with these molecular changes, Trrap deletion lengthens particularly G1 and S phases in APs in vivo. Therefore, our study reveals an essential and a distinct function of Trrap-HAT in regulation of cell cycle progression that is required for proper determination of neuroprogenitor fate. Determine gene transcriptions by comparing Trrap-deleted and wild type samples
2014-05-01 | E-GEOD-43650 | biostudies-arrayexpress
Project description:Epigenetic control of neural stem/progenitor cell fate is fundamental to achieve a fully brain architecture. Two intrinsic programs regulate neurogenesis, one by epigenetic-mediated gene transcription and another by cell cycle control. Whether and how these two are coordinated to determine temporally and spatially neural development remains unknown. Here we show that deletion of Trrap (Transcription translation associated protein), an essential cofactor for HAT (histone acetyltransferase), leads to severe brain atrophy due to a combination of cell death and a blockade of neuron production. Specifically, Trrap deletion forces differentiation of apical progenitor (AP) fate into basal progenitors (BP) and neurons thereby limiting the total neurogenic production. Despite Trrap’s general role in transcriptional regulation, a genome-wide transcriptome analysis of neuroprogenitors identified the cell cycle regulators that are specifically affected by Trrap deletion. Furthermore, E2F-dependent recruitment of HAT and transcription factors to the promoter of cell cycle regulators is impaired in Trrap-deleted neuroprogenitors. Consistent with these molecular changes, Trrap deletion lengthens particularly G1 and S phases in APs in vivo. Therefore, our study reveals an essential and a distinct function of Trrap-HAT in regulation of cell cycle progression that is required for proper determination of neuroprogenitor fate.
2014-05-01 | GSE43650 | GEO
Project description:The acetylation levels of histones and other proteins change during aging and have been linked to neurodegeneration. Here we show that deletion of the histone acetyltransferase (HAT) co-factor Trrap specifically impairs the function of the transcription factor Sp1, reduces its stability and causes a decrease in histone acetylation at Sp1 target genes. Modulation of Sp1 function by Trrap acts as a hub regulating multiple processes involved in neuron and neural stem cells function and maintenance including microtubule dynamics and the Wnt signaling pathway. Consistently, Trrap conditional mutants exhibit all hallmarks of neurodegeneration including dendrite retraction and axonal swellings, neuron death, astrogliosis, microglia activation, demyelination and decreased adult neurogenesis. Our results uncovered a novel functional network, essential to prevent neurodegeneration, and involving the specific regulation of Sp1 transcription factor and its downstream targets by Trrap-HAT.
2021-02-17 | GSE131283 | GEO
Project description:The acetylation levels of histones and other proteins change during aging and have been linked to neurodegeneration. Here we show that deletion of the histone acetyltransferase (HAT) co-factor Trrap specifically impairs the function of the transcription factor Sp1, reduces its stability and causes a decrease in histone acetylation at Sp1 target genes. Modulation of Sp1 function by Trrap acts as a hub regulating multiple processes involved in neuron and neural stem cells function and maintenance including microtubule dynamics and the Wnt signaling pathway. Consistently, Trrap conditional mutants exhibit all hallmarks of neurodegeneration including dendrite retraction and axonal swellings, neuron death, astrogliosis, microglia activation, demyelination and decreased adult neurogenesis. Our results uncovered a novel functional network, essential to prevent neurodegeneration, and involving the specific regulation of Sp1 transcription factor and its downstream targets by Trrap-HAT.
2021-02-17 | GSE131213 | GEO
Project description:The acetylation levels of histones and other proteins change during aging and have been linked to neurodegeneration. Here we show that deletion of the histone acetyltransferase (HAT) co-factor Trrap specifically impairs the function of the transcription factor Sp1 and the recruitment of HATs to Sp1 target genes. Modulation of Sp1 function by Trrap acts as a hub regulating multiple processes involved in neuron and neural stem cells function and maintenance including microtubule dynamics and the Wnt signaling pathway. Consistently, Trrap conditional mutants exhibit all hallmarks of neurodegeneration including dendrite retraction and axonal swellings, neuron death, astrogliosis, microglia activation, demyelination and decreased adult neurogenesis. Our results uncovered a novel functional network, essential to prevent neurodegeneration, and involving the specific regulation of Sp1 transcription factor by Trrap-HAT.
2021-03-02 | PXD013730 | Pride
Project description:Brain homeostasis is regulated by the viability and functionality of neurons. HAT (histone acetyltransferase) and HDAC (histone deacetylase) inhibitors have been applied to treat neurological deficits in humans; yet, the epigenetic regulation in neurodegeneration remains elusive. Mutations of HAT cofactor TRRAP (Transformation/translation domain-associated protein) cause human neuropathies, including psychosis, intellectual disability, autism and epilepsy, with unknown mechanism. Here we show that Trrap deletion in Purkinje neurons results in neurodegeneration of old mice. Integrated transcriptomics, epigenomics and proteomics reveal that TRRAP via SP1 conducts a conserved transcriptomic program. TRRAP is required for SP1 binding at the promoter proximity of target genes, especially microtubule dynamics. The ectopic expression of Stathmin3/4 ameliorates defects of TRRAP-deficient neurons, indicating that the microtubule dynamics is particularly vulnerable to the action of SP1 activity. This study unravels a network linking three well-known, but up-to-date unconnected, signaling pathways, namely TRRAP, HAT and SP1 with microtubule dynamics, in neuroprotection.
2021-03-02 | GSE131028 | GEO
Project description:Plant cells exhibit remarkable plasticity of their differentiation states, enabling regeneration of whole plants from differentiated somatic cells. How they revert cell fate and express pluripotency, however, remains unclear. Here we show that transcriptional activation of auxin biosynthesis is crucial for reprogramming differentiated leaf cells in Arabidopsis. We demonstrate that intervention of histone acetyltransferases causes severe defects in callus formation from leaf mesophyll protoplasts. Our data suggest that histone acetylation affects transcription of auxin biosynthesis genes. Auxin biosynthesis is in turn required to accomplish initial cell division through the activation of G2/M phase genes mediated by MYB DOMAIN PROTEIN 3-RELATED (MYB3Rs). We further show that AUXIN RESPONSE FACTOR 7 (ARF7)/ARF19 and INDOLE-3-ACETIC ACID INDUCIBLE 3 (IAA3)/IAA18-mediated auxin signaling pathway is responsible for the cell cycle reactivation in protoplasts. These findings provide novel mechanistic insights into how differentiated plant cells revert their fate and reinitiate the cell cycle to exert pluripotency.
2021-10-03 | GSE178645 | GEO
Project description:Matrix reverses immortalization-mediated stem cell fate determination
| PRJNA625241 | ENA
Project description:Establishment and maintenance of CNS glial cell identity ensures proper brain development and function, yet the epigenetic mechanisms underlying glial fate control remain poorly understood. Here we show that the histone deacetylase Hdac3 controls oligodendrocyte-specification gene Olig2 expression, and functions as a molecular switch for oligodendrocyte and astrocyte lineage determination. Our data suggest that Hdac3 cooperates with p300 to prime and maintain oligodendrogenic programs while inhibiting Stat3-mediated astrogliogenesis, and thereby regulate phenotypic commitment at the point of oligodendrocyte-astrocytic fate decision. Examination of Hdac3 and p300 genomewide occupancy in differentiating oligodendrocytes
2016-02-21 | E-GEOD-76411 | biostudies-arrayexpress