This SuperSeries is composed of the SubSeries listed below.
Mapping gene regulatory circuitry of Pax6 during neurogenesis.
Specimen part
View SamplesPax6 is a highly conserved transcription factor among vertebrates and is important in various aspects of the central nervous system (CNS) development. However, the gene regulatory circuitry of Pax6 underlying these functions remains elusive. We find that, following expression in neural progenitor cells, Pax6 targets many promoters embedded in an active chromatin environment. Intriguingly, many of these sites are also bound by another progenitor factor, Sox2, which cooperates with Pax6 in gene regulation. A combinatorial analysis of Pax6 binding dataset with transcriptome changes in Pax6-deficient neural progenitors reveals a dual role for Pax6, in which it activates the neuronal (ectodermal) genes while concurrently represses the mesodermal and endodermal genes thereby ensuring the unidirectionality of lineage commitment towards glutamatergic neuronal differentiation. Furthermore, Pax6 is critical for inducing activity of transcription factors that elicit neurogenesis and repress others that promote non-neuronal lineages. In addition to many established downstream effectors, Pax6 directly binds and activates a number of genes that are specifically expressed in neural progenitors but have not been previously implicated in neurogenesis. The in utero knockdown of one such gene, Ift74, during brain development impairs polarity and migration of new-born neurons. These findings demonstrate new aspects of the gene regulatory circuitry of Pax6, revealing how it functions to control neuronal development at multiple levels to ensure unidirectionality and proper execution of the neurogenic program.
Mapping gene regulatory circuitry of Pax6 during neurogenesis.
Specimen part
View SamplesRapid nerve conduction in the CNS is facilitated by the insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics is not well understood. Hypothesizing that only a fraction of all myelin-related mRNAs has been identified so far, we subjected myelin biochemically purified from mouse brains at various ages to RNA sequencing. We find a surprisingly large pool of transcripts abundant and/or enriched in myelin. Furthermore, a comprehensive analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting that the incorporation of mRNAs into the myelin compartment is highly selective. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months of age were minor. We suggest that this transcript pool provides a basis for the local modulation of myelin turnover and adaptation, i.e. in the individual internode. Overall design: A light-weight membrane fraction enriched for myelin was purified from mouse brains as described previously (Jahn et al., Neuromethods, 2013). For RNA-Seq, RNA was isolated from myelin of mice from indicated ages.
The transcriptome of mouse central nervous system myelin.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide analysis reveals a role for BRCA1 and PALB2 in transcriptional co-activation.
Specimen part, Disease, Cell line
View SamplesBreast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity.
Genome-wide analysis reveals a role for BRCA1 and PALB2 in transcriptional co-activation.
Specimen part, Cell line
View SamplesBreast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity.
Genome-wide analysis reveals a role for BRCA1 and PALB2 in transcriptional co-activation.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Requirement for SNAPC1 in transcriptional responsiveness to diverse extracellular signals.
Cell line, Treatment
View SamplesThe small nuclear RNA (snRNA)-activating protein complex (SNAPc) is a basal transcription factor that mediates the transcriptional activation of snRNAs. Here, we describe the genome-wide occupancy of the SNAPC1_and SNAPC4 subunits of SNAPc. While the SNAPC4 occupancy was in accord with the role for SNAPc in snRNA transcription, SNAPC1_displayed a broader genomic profile mirroring that of RNA polymerase II at highly active protein-coding genes. Our functional analysis revealed a role for SNAPC1_in regulation of both basal and activator-induced transcription of protein-coding genes. These studies expand the role for SNAPC1_beyond its regulation of snRNA transcription.
Requirement for SNAPC1 in transcriptional responsiveness to diverse extracellular signals.
Cell line, Treatment
View SamplesIn Arabidopsis, an individually darkened leaf (IDL) initiates senescence much quicker than a leaf from an entirely darkened plant (DP).
Darkened Leaves Use Different Metabolic Strategies for Senescence and Survival.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Krüppel-like factor 4 (KLF4) inactivation in chronic lymphocytic leukemia correlates with promoter DNA-methylation and can be reversed by inhibition of NOTCH signaling.
Sex
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