WormMine: Gene WBGene00001964

• WormBase Gene ID: WBGene00001964
• Gene Name: hlh-25
• Sequence Name: C17C3.7
• Brief Description: hlh-25 encodes a REF-1-like protein with two bHLH domains that partially represses lag-2 transcription in ABa descendants (in response to a Notch signal, redundantly with HLH-27); lag-2 repression by HLH-25 may require UNC-37; HLH-25's paralogs include HLH-26 through HLH-29 and (more distantly) REF-1; hlh-25 is transcribed in the early MS lineage, has clustered binding sites for MED-1/2 in its promoter region, can be activated by ectopic MED-1, and loses activity in MED-1/2-deficient genetic backgrounds; HLH-25 is expressed in ABp granddaughters ~25 minutes after ABp first contacts an APX-1-expressing cell, and in ABa descendants after a second Notch interaction; HLH-25 is also expressed in four EMS granddaughters (MSaa, MSap, MSpa, MSpp) beginning at the 24-cell stage; ectopic HLH-25 can induce body muscle development in skn-1(RNAi);pal-1(RNAi) embryos that would otherwise lack muscle; HLH-25 is required for embryonic viability in mass RNAi assays.
• Organism: Caenorhabditis elegans
• Automated Description: Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including dauer exit; determination of adult lifespan; and negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Expressed in several structures, including MSpa; anal depressor muscle; body wall musculature; intestinal cell; and neurons.
• Biotype: SO:0001217
• Genetic Position: II :-1.19086 ±0.002255
• Length (nt): 1167

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00001964

Genomics

1 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:C17C3.7.1	C17C3.7.1	1064	II: 5535239-5536405

Other

1 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:C17C3.7	C17C3.7	807	II: 5535240-5535397

7 RNAi Result

• WBRNAi00040773
• WBRNAi00040785
• WBRNAi00010899
• WBRNAi00010905
• WBRNAi00024579
• WBRNAi00027179
• WBRNAi00084010

12 Allele

• gk963801
• gk963053
• gk963389
• WBVar01603876
• tm432
• WBVar01898525
• ok1710
• WBVar01306082
• WBVar02084798
• WBVar02002685
• WBVar01306081
• WBVar02017927

1 Chromosome

• WormBase ID: II
• Organism: Caenorhabditis elegans
• Length (nt): 15279421

1 Chromosome Location

• Feature . Primary Identifier: WBGene00001964
• Start: 5535239
• End: 5536405
• Strand: 1

4 Data Sets

• WormBaseAcedbConverter
• GO Annotation data set
• C. elegans genomic annotations (GFF3 Gene)
• Panther orthologue and paralogue predictions

1 Downstream Intergenic Region

• WormBase ID: intergenic_region_chrII_5536406..5537823
• Length (nt): 1418
• Chromosome Location: II: 5536406-5537823
• Organism: Caenorhabditis elegans

33 Expression Clusters

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Coexpression clique No. 203, sre-33-ZK1025.1_8337, on the genome-wide coexpression clique map for the nematode GPL200 platform.	All available microarray datasets for the GPL200 platform (Affymetrix C. elegans Genome Array) were obtained from the GEO repository. This included 2243 individual microarray experiments. These were normalized against each other with the software RMAexpress (Bolstad, 2014). Based on these normalized values, Pearsons correlation coefficients were obtained for each probe-probe pair of the 22,620 probes represented on this array type. The resulting list of correlation coefficients was then ranked to generate the ranked coexpression database with information on each probe represented on the GPL200 platform.	WBPaper00061527:sre-33-ZK1025.1_8337
	Transcripts that showed significantly increased expression in whole animal day 1 N2 adults comparing to in whole animal day 8 N2 adults.	DESeq2, FDR < 0.05, fold change > 2.	WBPaper00066978:Day1Adult_vs_Day8Adult_upregulated_neuron
	Transcripts of coding genes that showed significantly increased expression in muscle.	DESeq2 (version 1.24.0). Transcripts with a false-discovery rate adjusted p-value less than 0.05 were considered significantly differentially expressed.	WBPaper00062325:muscle_enriched_coding-RNA
	Transcripts that showed significantly increased expression in set-2(tm1630) animals at embryo stage, comparing to in N2 animals.	DESeq2 (v2.1.8.3) was used to determine DE genes and to generate principal component and scatter plots. DE genes with FDR < 0.05 were analysed using g:Profiler with Bonferroni correction.	WBPaper00060014:set-2(tm1630)_upregulated
	Embryonic class (E): genes that significantly increase in abundance at some point during embryogenesis.	A modified Welch F statistic was used for ANOVA. For each gene, regressed error estimates were substituted for observed error estimates. The substitution is justified by the lack of consistency among the most and least variable genes at each time point. Regressed error estimates were abundance-dependent pooled error estimates that represented a median error estimate from a window of genes of similar abundance to the gene of interest. A randomization test was used to compute the probability Pg of the observed F statistic for gene g under the null hypothesis that developmental time had no effect on expression. P-values were not corrected for multiple testing.	[cgc5767]:expression_class_E
	Strictly embryonic class (SE): genes that are the subset of embryonic genes that are not also classified as maternal.	A modified Welch F statistic was used for ANOVA. For each gene, regressed error estimates were substituted for observed error estimates. The substitution is justified by the lack of consistency among the most and least variable genes at each time point. Regressed error estimates were abundance-dependent pooled error estimates that represented a median error estimate from a window of genes of similar abundance to the gene of interest. A randomization test was used to compute the probability Pg of the observed F statistic for gene g under the null hypothesis that developmental time had no effect on expression. P-values were not corrected for multiple testing.	[cgc5767]:expression_class_SE
Bacteria infection: Photorhabdus luminescens	Genes with increased expression after 24 hours of infection by P.lumniescens Fold changes shown are pathogen vs OP50.	For RNA-seq and tiling arrays, log2 fold changes between gene expression values of infected versus uninfected nematodes were calculated. For log2 fold changes > 0.00001 the values > 81.25th percentile were defined as up-regulated and for log2 fold changes < -0.00001 the values < 18.75th percentile were defined as down-regulated.	WBPaper00038438:P.lumniescens_24hr_upregulated_TilingArray
	Genes down-regulated after 24 hour exposure to colistin.	Gene lists were created using a cutoff P-value of < 0.05, 2-fold change.	WBPaper00045673:colistin_downregulated
	Embryonic transient class (ET): genes that are the subset of embryonic genes in which the latest significant increase is earlier than their latest significant decrease.	A modified Welch F statistic was used for ANOVA. For each gene, regressed error estimates were substituted for observed error estimates. The substitution is justified by the lack of consistency among the most and least variable genes at each time point. Regressed error estimates were abundance-dependent pooled error estimates that represented a median error estimate from a window of genes of similar abundance to the gene of interest. A randomization test was used to compute the probability Pg of the observed F statistic for gene g under the null hypothesis that developmental time had no effect on expression. P-values were not corrected for multiple testing.	[cgc5767]:expression_class_ET
	Transcripts that showed significantly decreased expression in hda-2(ok1479) comparing to in N2 animals.	DESeq2 (version 1.28.1), FDR < 0.01, fold change > 2.	WBPaper00062159:hda-2(ok1479)_downregulated
	Transcripts that showed significantly decreased expression glp-1(e2141); TU3401 animals comparing to in TU3401 animals.	Fold change > 2, FDR < 0.01.	WBPaper00065993:glp-1(e2141)_downregulated
	Transcripts that showed significantly decreased expression after animals were treated with 100uM Rapamycin, 50uM Rifampicin and 100uM Psora from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rapamycin-Rifampicin-Psora_downregulated
	Strictly embryonic transient class (SET): genes that are the subset of embryonic transient genes that are not also classified as maternal.	A modified Welch F statistic was used for ANOVA. For each gene, regressed error estimates were substituted for observed error estimates. The substitution is justified by the lack of consistency among the most and least variable genes at each time point. Regressed error estimates were abundance-dependent pooled error estimates that represented a median error estimate from a window of genes of similar abundance to the gene of interest. A randomization test was used to compute the probability Pg of the observed F statistic for gene g under the null hypothesis that developmental time had no effect on expression. P-values were not corrected for multiple testing.	[cgc5767]:expression_class_SET
	Transcripts that showed significantly decreased expression in daf-2(e1370) comparing to in N2.	Student's t-test, fold change > 2, p-value < 0.05.	WBPaper00055386:daf-2(e1370)_downregulated
	Transcripts that showed significantly decreased expression in mrps-5(RNAi) comparing to in control animals.	Fold change > 4, p-value < 0.01	WBPaper00056330:mrps-5(RNAi)_downregulated
	Genes that showed significantly increased expression after exposure to adsorbable organic bromine compounds (AOBr) contained in M. aeruginosa batch culture.	Differentially expressed genes (DEGs) were identified with a random variance t-test and a significance analysis of microarrays (SAM) test. Genes were considered statistically significant if their p-value was less than 0.05, the false discovery rate less than 0.3, and the fold change compared to control at least <= 0.67 or >=1.5.	WBPaper00046853:AOBr_M.aeruginosa-batch-culture_upregulated
	Genes with changed expression in lin-54(n2290) embryo.	To determine differentially expressed genes between wild-type and mutants, moderated T Statistics in limma was used with p-value <= 0.01, fold change >= 1.5.	WBPaper00038427:lin-54_embryo_changed
	Genes from N2 animals with significantly increased expression after 72 hours of treatment on growth media with 250uM allantoin in 2% DMSO.	Analysis of gene expression data was carried out with the Affymetrix Transcriptome Analysis Console. Data preprocessing (using RMA normalization) and QC metrics were performed using Affymetrix Expression Console TM and manually inspected afterwards. Expression analysis was carried out for each two pairwise conditions. FDR statistical correction for multiple testing resulted in a slightly lower number of DEGs in most cases. P-value < 0.05 and fold change > 2.0 were used to determine differentially expressed genes.	WBPaper00048989:N2_allantoin_upregulated
	Transcripts that showed significantly increased expression in DA116[eat-2(ad1116)] comparing to in N2.	The DESeq2 package (v1.24.0) was used to identify differentially expressed genes (DEGs). Fold change > 2, FDR < 0.05.	WBPaper00061040:eat-2(ad1116)_upregulated
	C-lineage related expression profile.	QT clustering	WBPaper00025032:cluster_134
	Embryonic (E) subclasses are based on the earliest significant increase(abbreviated pi for primary increase).	A modified Welch F statistic was used for ANOVA. For each gene, regressed error estimates were substituted for observed error estimates. The substitution is justified by the lack of consistency among the most and least variable genes at each time point. Regressed error estimates were abundance-dependent pooled error estimates that represented a median error estimate from a window of genes of similar abundance to the gene of interest. A randomization test was used to compute the probability Pg of the observed F statistic for gene g under the null hypothesis that developmental time had no effect on expression. P-values were not corrected for multiple testing.	[cgc5767]:expression_class_E_pi(23_min)
Bacteria diet: Chryseobacterium sp. CHNTR56 MYb120	Transcripts that showed significantly decreased expression after animals were fed by Chryseobacterium sp. CHNTR56 MYb120, comparing to animals fed by OP50.	edgeR FDR <= 0.05, fold change >= 4.	WBPaper00061424:Diet_MYb120_downregulated
	Transcripts that showed significantly decreased expression in sin-3(tm1276) comparing to in N2.	DESeq2, fold change > 2, p-value < 0.01.	WBPaper00061203:sin-3(tm1276)_downregulated
	Transcripts that showed significantly decreased expression in spr-1(ok2144) comparing to in N2.	DESeq2, fold change > 2, p-value < 0.01.	WBPaper00061203:spr-1(ok2144)_downregulated
	Transcripts that showed significantly increased expression in sin-3(tm1276) comparing to in N2 at early embryo when there were only 3 -5 eggs in the adult.	DESeq2, fold change > 2, adjusted p-value < 0.01	WBPaper00058598:sin-3(tm1276)_upregulated
	Genome-wide analysis of developmental and sex-regulated gene expression profile.	self-organizing map	cgc4489_group_21
	Embryonic transient (ET) subclasses are based on time of max abundance.	A modified Welch F statistic was used for ANOVA. For each gene, regressed error estimates were substituted for observed error estimates. The substitution is justified by the lack of consistency among the most and least variable genes at each time point. Regressed error estimates were abundance-dependent pooled error estimates that represented a median error estimate from a window of genes of similar abundance to the gene of interest. A randomization test was used to compute the probability Pg of the observed F statistic for gene g under the null hypothesis that developmental time had no effect on expression. P-values were not corrected for multiple testing.	[cgc5767]:expression_class_ET_max(41_min)
	Transcripts that showed significantly increased expression in ash-2(RNAi) comparing to in wild type animals injected with vector.	Differential mRNA expression using DESeq2. mRNAs with a FDR < 0.05 and fold change > 2 considered differentially expressed.	WBPaper00066232:ash-2(RNAi)_upregulated_WT
	Top 300 transcripts enriched in ADEshL, ADEshR according to single cell RNAseq.	Top 300 enriched transcripts were determined by log2.ratio of the tpm in the cell type vs the tpm in the other cells * the log2 of the cell.type tpm.	WBPaper00061340:ADEsh
	Genes up-regulated greater than 2-fold by Cu2+ in wild-type animals, by comparing transcript expression levels between animals with or without Cu2+ treatment.	N.A.	WBPaper00042067:Cu2+_upregulated_WT

6 Expression Patterns

• Primary Identifier: Expr8067
• Pattern: hlh-25 was expressed in four of the EMS granddaughters (MSaa, MSap, MSpa, Mspp). Approximately 25 min after ABp first contacts a ligand-expressing cell at the four-cell stage, all ref-1 family members were expressed in the ABp granddaughters. No expression was detected in ABa descendants or descendants of other early blastomeres such as EMS or P3. The second Notch interaction begins at the 12-cell stage, when two of the four ABa descendants contact a ligand-expressing cell. The ref-1 family was expressed about 25 min later in the daughters of the two Notch-activated ABa descendants, but not in other ABa descendants; these same embryos continued to show expression in the ABp descendants activated by the first interaction.

• Primary Identifier: Expr12501
• Pattern: hlh-25::GFP was expressed at all larval and adult stages, including dauer stage, in unidentified neurons of the head and tail, the anal depressor muscle, anterior and posterior intestinal cells, and the head and body wall muscles of transgenic animals. Expression was detected in the PDE sensory neuron pairs and rarely, transient expression was observed in migrating distal tip cells of L3/L4 stage animals.

• Primary Identifier: Expr3495
• Pattern: Expressed in: early MS lineage

• Primary Identifier: Expr2030739
• Pattern: Single cell embryonic expression. Only cell types with an expression fraction of greater 0.2 of the maximum expressed fraction are labeled (Full data can be downloaded from http://caltech.wormbase.org/pub/wormbase/datasets-published/packer2019/). The colors represent the broad cell class to which the cell type has been assigned. The size of the point is proportional to the log2 of the numbers of cells in the dataset of that cell type. Interactive visualizations are available as a web app (https://cello.shinyapps.io/celegans/) and can also be installed as an R package (https://github.com/qinzhu/VisCello.celegans).

• Primary Identifier: Expr1144824
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr2012500
• Pattern: Single cell embryonic expression. Only cell types with an expression fraction of greater 0.2 of the maximum expressed fraction are labeled (Full data can be downloaded from http://caltech.wormbase.org/pub/wormbase/datasets-published/packer2019/). The colors represent the broad cell class to which the cell type has been assigned. The size of the point is proportional to the log2 of the numbers of cells in the dataset of that cell type. Interactive visualizations are available as a web app (https://cello.shinyapps.io/celegans/) and can also be installed as an R package (https://github.com/qinzhu/VisCello.celegans).

14 GO Annotation

51 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00001964
• Start: 5535239
• End: 5536405
• Strand: 1

14 Ontology Annotations

2 Regulates Expr Cluster

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Genes down regulated by 2.0 fold or greater in hlh-25(ok1710) mutants.	The Students t-test was performed to find the candidates for differential expression, and genes with significant signal level between different conditions (P < 0.05) were collected. In addition, fold change analysis were performed on the genes with significant expression, and all genes showing greater than two-fold change were considered putative targets.	WBPaper00048624:hlh-25(ok1710)_downregulated
	Genes up regulated by 2.0 fold or greater in hlh-25(ok1710) mutants.	The Students t-test was performed to find the candidates for differential expression, and genes with significant signal level between different conditions (P < 0.05) were collected. In addition, fold change analysis were performed on the genes with significant expression, and all genes showing greater than two-fold change were considered putative targets.	WBPaper00048624:hlh-25(ok1710)_upregulated

1 Sequence

• Length: 1167

1 Sequence Ontology Term

• Name: gene

1 Strains

• WBStrain00036426

1 Upstream Intergenic Region

• WormBase ID: intergenic_region_chrII_5533743..5535238
• Length (nt): 1496
• Chromosome Location: II: 5533743-5535238
• Organism: Caenorhabditis elegans