Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of transcriptional targets of a network of Drosophila core promoter factors in neural stem cells

ABSTRACT: The transcriptional mechanisms that allow neural stem cells (NSC) to balance self-renewal with differentiation are not well understood. We identify here a unique subset of TATA -binding protein associated factors (TAFs) as NSC identity genes in Drosophila. We found that depletion of any one of nine TAFs or the TBP-related factor 2 (TRF2), resulted in fewer NSCs exhibiting delayed cell cycle progression without impacting NSC survival. In contrast, depletion of TBP led to a delay in NSC cell cycle progression without loss of self-renewal. An integrated RNA-seq and DamID analysis revealed that TAFs function with both TBP and TRF2, and that TAF-TBP and TAF-TRF2 shared targets genes encode different subsets of transcription factors and RNA-binding proteins with established or emerging roles in NSC identity and brain development. Taken together, our results demonstrate that core promoter factors are selectively required for NSC identity in vivo by promoting cell cycle progression, NSC cell polarity and by preventing premature differentiation. Because pathogenic variants in TAF1, TAF2, TAF6, TAF8 and TAF13 have all been linked to human neurological disorders, this work may stimulate and inform future animal models of TAF-linked neurological disorders.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE120430 | GEO | 2019/04/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of genomic binding sites of a network of core promoter factors in developing Drosophila brains

Project description:The transcriptional mechanisms that allow neural stem cells (NSC) to balance self-renewal with differentiation are not well understood. We identify here a unique subset of TATA -binding protein associated factors (TAFs) as NSC identity genes in Drosophila. We found that depletion of any one of nine TAFs or the TBP-related factor 2 (TRF2), resulted in fewer NSCs exhibiting delayed cell cycle progression without impacting NSC survival. In contrast, depletion of TBP led to a delay in NSC cell cycle progression without loss of self-renewal. An integrated RNA-seq and DamID analysis revealed that TAFs function with both TBP and TRF2, and that TAF-TBP and TAF-TRF2 shared targets genes encode different subsets of transcription factors and RNA-binding proteins with established or emerging roles in NSC identity and brain development. Taken together, our results demonstrate that core promoter factors are selectively required for NSC identity in vivo by promoting cell cycle progression, NSC cell polarity and by preventing premature differentiation. Because pathogenic variants in TAF1, TAF2, TAF6, TAF8 and TAF13 have all been linked to human neurological disorders, this work may stimulate and inform future animal models of TAF-linked neurological disorders.

2019-04-01 | GSE120432 | GEO

ChIP-chip from H9 hESCs for RNA Polymerase II, TBP, TAF3, TAF5, TAF7, and TAF11

Project description:The general transcription factor TFIID is composed of the TATA-box-binding protein (TBP) and approximately 14 TBP-associated factors (TAFs). Here we find, unexpectedly, that undifferentiated human embryonic stem cells (hESCs) contain only six TAFs (TAFs 2, 3, 5, 6, 7 and 11), whereas following differentiation all TAFs are expressed. Directed and global chromatin immunoprecipitation analyses reveal an unprecedented promoter occupancy pattern: most active genes are bound by only TAFs 3 and 5 along with TBP, whereas the remaining active genes are bound by TBP and all six hESC TAFs. Consistent with these results, hESCs contain a previously undescribed complex containing TAFs 2, 6, 7, 11 and TBP. Altering the composition of hESC TAFs, either by depletion of TAFs that are present or ectopic expression of TAFs that are absent, results in misregulation of pluripotency gene expression and induction of differentiation. Thus, the selective expression and use of TAFs underlies the ability of hESCs to self-renew. ChIP-chip was used in this study to assess the global pattern of TAF recruitment at a gene promoters, to verify the existence of two classes of genes which differentially recruit and use TAF proteins for transcription initiation. Comparison of recruitment of 4 TAFs (TAF3, TAF5, TAF7 and TAf11) with the recruitment of TBP and RNA Polymerase II in wild-type H9 embryonic stem cells from replicate experiments

2012-11-19 | E-GEOD-39312 | biostudies-arrayexpress

ChIP-chip from H9 hESCs for RNA Polymerase II, TBP, TAF3, TAF5, TAF7, and TAF11

2012-11-19 | GSE39312 | GEO

Genome-wide regulation by TFIID and SAGA

Project description:TFIID and SAGA share a common set of TAFs, regulate chromatin, and deliver TBP to promoters. Here we examine their relationship within the context of the Saccharomyces cerevisiae genome-wide regulatory network. We find that while TFIID and SAGA make overlapping contributions to the expression of all genes, TFIID function predominates at ~90% and SAGA at ~10% of the measurable genome. Strikingly, SAGA-dominated genes are largely stress-induced and TAF-independent, and are down-regulated by the coordinate action of a variety of chromatin, TBP, and RNA polymerase II regulators. In contrast, the TFIID-dominated class is less regulated, but is highly dependent upon TAFs including those shared between TFIID and SAGA. These two distinct modes of transcription regulation might reflect the need to balance inducible stress responses with the steady output of housekeeping genes. Keywords = Taf1 Keywords = Spt3 Keywords = Gcn5

2004-02-26 | E-GEOD-885 | biostudies-arrayexpress

Genome-wide regulation by TFIID and SAGA

2004-02-27 | GSE885 | GEO

Genome-wide localization of Trf2 and TBP in Drosophila embryos

Project description:Here we use ChIP-seq in Drosophila embryos to determine the genome-wide binding pattern of TBP and Trf2 using two different antibodies for each factor. ChIP-seq using anti-Trf2 and anti-TBP antibodies in Drosophila embryos

2014-06-04 | E-GEOD-52029 | biostudies-arrayexpress

TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ ALF to promote haploid cell gene expression [ChIP-seq]

Project description:TRF2 is a paralogue of TATA-box binding protein (TBP) with highest expression in testis. Although Trf2 inactivation in mice leads to arrested spermatogenesis, there is no direct evidence that Trf2 is recruited to chromatin to directly regulate gene expression. We used genetically modified mice where endogenous Trf2 has been modified to carry a TAP-TAG to perform ChIP-reChIP followed by deep sequencing. We found that Trf2 is recruited to all active promoters as a subunit of TFIIA/ALF complex together with TBP.

2016-08-31 | GSE79601 | GEO

scRNA of GBM tumors

Project description:Glioblastoma (GBM) presents a formidable clinical challenge due to its complex microenvironment. Here, we introduce tumor-associated foam cells (TAFs), a previously unidentified immune cell entity of lipid droplet (LD)-loaded macrophages, in GBM. Through extensive analyses of patient tumors, together with in vitro and in vivo investigations, we reveal that TAFs exhibit distinct pro-tumorigenic characteristics related to hypoxia, mesenchymal transition, angiogenesis, and impaired phagocytosis. Moreover, TAF presence correlates with worse patient outcome. Our mechanistic investigations demonstrate that TAF formation is facilitated by lipid cargo transfer from extracellular vesicles released by GBM cells. Importantly, we demonstrate that targeting key enzymes involved in LD formation, such as DGAT1 or ACSL, effectively disrupts TAF functionality. This study establishes TAFs as a prominent immune cell entity in GBM and provides valuable insights into their interplay within the microenvironment. Disrupting LD formation to target TAFs presents an interesting avenue for future therapeutic development in GBM.

2023-08-16 | GSE237673 | GEO

RNA-seq analysis of testis transcripts from Wt and Trf2-/- mice [RNA-seq]

2016-08-31 | GSE79602 | GEO

Taf7l cooperates with Trf2 to regulate spermiogenesis

Project description:Taf7l (a paralogue of Taf7) and Trf2 (a TBP-related protein) are components of the core promoter complex required for gene/tissue-specific transcription of protein-coding genes by RNA polymerase II. Previous studies reported that Taf7l knockout mice exhibit structurally abnormal sperm, reduced sperm count, weakened motility and compromised fertility. Here we find that continued backcrossing of Taf7l-/Y mice from N5 to N9 produced KO males that are essentially sterile. Genome-wide expression profiling by mRNA-seq analysis of wild type (WT) and Taf7l-/Y (KO) testes revealed that Taf7l ablation impairs the expression of many post-meiotic spermatogenic specific as well as metabolic genes. Importantly, histological analysis of testes revealed that Taf7l-/Y mice develop post-meiotic arrest at the first stage of spermiogenesis, phenotypically similar to Trf2-/- mice, but distinct from Taf4b-/- mice. Indeed, we find that Taf7l and Trf2 co-regulate post-meiotic genes, but none of Taf4b-regulated germ stem cell genes in testes. Genome-wide ChIP-seq studies indicate that TAF7L binds to promoters of activated post-meiotic genes in testis. Moreover, biochemical studies show that TAF7L associates with TRF2 both in vitro and in testis suggesting that TAF7L likely cooperates directly with TRF2 at promoters of a subset of post-meiotic genes to regulate spermiogenesis. Our findings thus provide a new mechanism for cell-type specific transcriptional control involving an interaction between a ‘non-prototypic’ core promoter recognition factor (Trf2) and an orphan TAF subunit (Taf7l) in mammalian testis-specific gene transcription. Genome-wide mapping of TAF7L and Pol II in testis tissue, and mRNA-seq expression profiling wild type and Taf7l knockout testis.

2013-09-29 | E-GEOD-50807 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data