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Phylogenetic & expression analysis of the bHLH transcription factor family: genomic approach to cellular differentiation

ABSTRACT: A phylogenetic analysis of seven different species (human, mouse, rat, worm, fly, yeast, and plant) utilizing all (541) basic helix-loop-helix (bHLH) genes identified, including expressed sequence tags (EST), was performed. A super-tree involving six clades and a structural categorization involving the entire coding sequence was established. A nomenclature was developed based on clade distribution to discuss the functional and ancestral relationships of all the genes. The position/location of specific genes on the phylogenetic tree in relation to known bHLH factors allows for predictions of the potential functions of uncharacterized bHLH factors, including EST's. A genomic analysis using microarrays for four different mouse cell types (i.e. Sertoli, Schwann, thymic, and muscle) was performed and considered all known bHLH family members on the microarray for comparison. Cell-specific groups of bHLH genes helped clarify those bHLH genes potentially involved in cell specific differentiation. This phylogenetic and genomic analysis of the bHLH gene family has revealed unique aspects of the evolution and functional relationships of the different genes in the bHLH gene family. PMID: 18557763 We used microarrays to determine bHLH expression in 20d rat Sertoli cells.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE20259 | GEO | 2010/02/11

SECONDARY ACCESSION(S): PRJNA124223

REPOSITORIES: GEO

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Phylogenetic & expression analysis of the bHLH transcription factor family: genomic approach to cellular differentiation

Project description:A phylogenetic analysis of seven different species (human, mouse, rat, worm, fly, yeast, and plant) utilizing all (541) basic helix-loop-helix (bHLH) genes identified, including expressed sequence tags (EST), was performed. A super-tree involving six clades and a structural categorization involving the entire coding sequence was established. A nomenclature was developed based on clade distribution to discuss the functional and ancestral relationships of all the genes. The position/location of specific genes on the phylogenetic tree in relation to known bHLH factors allows for predictions of the potential functions of uncharacterized bHLH factors, including EST's. A genomic analysis using microarrays for four different mouse cell types (i.e. Sertoli, Schwann, thymic, and muscle) was performed and considered all known bHLH family members on the microarray for comparison. Cell-specific groups of bHLH genes helped clarify those bHLH genes potentially involved in cell specific differentiation. This phylogenetic and genomic analysis of the bHLH gene family has revealed unique aspects of the evolution and functional relationships of the different genes in the bHLH gene family. PMID: 18557763 We used microarrays to determine bHLH expression in 20d rat Sertoli cells. RNA samples from two control groups (Sertoli cells cultured for 72 h) are compared to two treated groups (Sertoli cells cultured for 72 h with cAMP).

2010-02-21 | E-GEOD-20259 | biostudies-arrayexpress

Local Genomic Features Predict the Distinct and Overlapping Binding Patterns of the bHLH‐Zip Family Oncoproteins MITF and MYC‐MAX

Project description:MITF and MYC are well‐known oncoproteins and members of the basic helix‐loop‐helix leucine zipper (bHLH‐Zip) family of transcription factors (TFs) recognizing hexamer E‐box motifs. MITF and MYC not only share the core binding motif, but are also the two most highly expressed bHLH‐Zip transcription factors in melanocytes, raising the possibility that they may compete for the same binding sites in select oncogenic targets. Mechanisms determining the distinct and potentially overlapping binding modes of these critical oncoproteins remain uncharacterized. We introduce computational predictive models using local sequence features, including a boosted convolutional decision tree framework, to distinguish MITF vs. MYC‐MAX binding sites with up to 80% accuracy genome wide. Select E‐box locations that can be bound by both MITF and MYC‐MAX form a separate class of MITF binding sites characterized by differential sequence content in the flanking region, diminished interaction with SOX10, higher evolutionary conservation, and less tissue‐specific chromatin organization.

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Basic helix-loop-helix transcription factor Tcf21 is downstream target of male sex-determining gene SRY

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DNA binding specificity for the bHLH-PAS transcription factor family

Project description:Transcription factor-DNA interactions and their specificities have been described for many different classes of transcription factor families. However, heterodimeric transcription factor complexes still remain poorly characterised. The basic-Helix-Loop-Helix (bHLH) transcription factor family is one of the largest transcription factor families that typically bind DNA though a degenerate CANNTG elements as heterodimers or homodimers. Here we characterise the DNA binding of the bHLH - Per-Arnt-Sim (PAS) (bHLH-PAS) domain containing transcription factor family using SELEX-high-throughput sequencing coupled with quantitative computational modelling analysis. We show that most dimeric bHLH-PAS transcription factors bind to distinct core NNCGTG response elements but bind over a much larger footprint than previously characterised. Modelled DNA-protein interactions were found to correlate with structural analysis, DNA shape predictions and in vivo transcription factor occupancy.

2022-07-02 | GSE159989 | GEO

Arnt2 tunes activity-dependent gene expression through NCoR2-mediated repression and Npas4-mediated activation

Project description:ChIP-, ATAC-, and RNA-seq data Neuronal activity-dependent transcription is tuned to ensure precise gene induction during periods of heightened synaptic activity, allowing for appropriate responses of activated neurons within neural circuits. The consequences of aberrant induction of activity-dependent genes on neuronal physiology are not yet clear. Here, we demonstrate that, in the absence of synaptic excitation, the basic-helix-loop-helix (bHLH)-PAS family transcription factor ARNT2 recruits the NCoR2 co-repressor complex to suppress neuronal activity-dependent regulatory elements and maintain low basal levels of inducible genes. This restricts inhibition of excitatory neurons, maintaining them in a state that is receptive to future sensory stimuli. By contrast, in response to heightened neuronal activity, ARNT2 recruits the neuronal-specific bHLH-PAS factor NPAS4 to activity-dependent regulatory elements to induce transcription and thereby increase somatic inhibitory input. Thus, the interplay of bHLH-PAS complexes at activity-dependent regulatory elements maintains temporal control of activity-dependent gene expression and scales somatic inhibition with circuit activity.

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Basic helix-loop-helix transcription factor Tcf21 is downstream target of male sex-determining gene SRY

Project description:The cascade of molecular events involved in mammalian sex determination has been shown to involve the SRY gene, but specific downstream events have eluded researchers for decades. The current study identifies one of the first direct downstream targets of the male sex-determining factor SRY as the basic-helix-loop-helix (bHLH) transcription factor TCF21. SRY was found to directly associate with the Tcf21 promoter SRY/SOX9 response element both in vitro and in vivo during male sex determination. TCF21 was found to promote an in vitro sex reversal of embryonic ovarian cells to promote precursor Sertoli cell differentiation. Therefore, SRY acts directly on the Tcf21 promoter to, in part, initiate a cascade of events associated with Sertoli cell differentiation and embryonic testis development. We used microarrays to determine genes whose expression was stimulated in rat E13 ovarian cell sub-cultures in the presence of a pCMV-myc-expression plasmid over-expressing the Sry, Tsf21, and/or Tcf12 (Reb-alfa) genes. RNA samples from the control group (untreated E13 rat ovarian cells) are compared to RNA from 4 groups of treated E13 rat ovarian cells: 1) Sry overexpressing, 2) Tcf21 overexpressing, 3) Tcf12 (Reb alfa) overexpressing, and 4) Tcf21 + Tcf12 (Reb-alfa) overexpressing. Untreated E13 testis cell sub-cultures were also analyzed. 3 biological replicates each group.

2011-04-25 | E-GEOD-24666 | biostudies-arrayexpress

bHLH Transcription Factors that Facilitate K+ Uptake During Stomatal Opening are Repressed by Abscisic Acid through Phosphorylation

Project description:Stomata open in response to light and close following exposure to abscisic acid (ABA). They regulate gas exchange between plants and atmosphere, allowing plants to adapt to changing environmental conditions. ABA binding to receptors initiates a signaling cascade that involves protein phosphorylation. Here we show that ABA induced phosphorylation of three basic helix-loop-helix (bHLH) transcription factors, called AKSs (ABA-RESPONSIVE KINASE SUBSTRATES; AKS1, AKS2, AKS3), in Arabidopsis guard cells, and that they facilitated stomatal opening through the transcription of genes encoding inwardly-rectifying K+ channels. aks1aks2-1 double mutant plants showed decreases in light-induced stomatal opening, K+ accumulation in response to light, activity of inwardly-rectifying K+ channels, and transcription of genes encoding major inwardly-rectifying K+ channels without affecting ABA-mediated stomatal closure. Overexpression of POTASSIUM CHANNEL IN ARABIDOPSIS THALIANA 1 (KAT1), which encodes a major inwardly-rectifying K+ channel in guard cells, rescued the phenotype of aks1aks2-1 plants. AKS1 bound directly to the promoter of KAT1, an interaction that was attenuated after ABA-induced phosphorylation. The ABA agonist pyrabactin induced phosphorylation of AKSs. Our results demonstrate that the AKS family of bHLH transcription factors facilitates stomatal opening through transcription of genes encoding inwardly-rectifying K+ channels, and that ABA suppresses the activity of inwardly-rectifying K+ channel activity by triggering the phosphorylation of these transcription factors. Microarray data have been deposited in the Gene Expression Omnibus with accession number: GSE46574.

2013-06-28 | PXD000235 | Pride

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Project description:The hlh-30 gene encodes a C. elegans basic-helix-loop-helix (bHLH) transcription factor; We compared RNA from wild type worms and worms mutant for the hlh-30 gene to identify putative target genes of the HLH-30 transcription factor.

2009-07-24 | GSE15762 | GEO

Transcription profiling of E47 targets in the neuroblastoma cell line SK-N-SH at 8 hours and 20 hours

Project description:E47 is a basic Helix Loop Helix (bHLH) transcription factor that has important roles in cell fate determination and differentiation of many cell types. In the nervous system E47 heterodimerizes with tissue-specific, pro-neural bHLH transcription factors and activates downstream target genes. To identify the relevant target genes of bHLH transcription factors in neural cells, we performed gene expression profiling of the human neuroblastoma cell line SK-N-SH engineered to acutely express ectopic E47 by an adenoviral vector. The experiments were done at two time points following adenoviral infection, 8 hours and 20 hours. Genes induced by E47 after 8 hours are likely to be direct targets of this transcription factor.

2006-02-01 | E-MEXP-413 | biostudies-arrayexpress

Olig2 targetome in SHH subgroup of medulloblastoma

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