WormMine: Gene WBGene00003605

• WormBase Gene ID: WBGene00003605
• Gene Name: nhr-6
• Sequence Name: C48D5.1
• Brief Description: nhr-6 encodes a nuclear receptor of the NR4A subfamily that is orthologous to the mammalian NGFI-B receptors and the Drosophila HR38 nuclear receptor (DHR38) that has been implicated in molting and metamorphosis; nhr-6 activity is required for spermatheca development and thus, for regulation of ovulation and fertilization; a GST-NHR-6 fusion protein can bind the canonical vertebrate NR4A binding sequence in vitro and activate transcription from a reporter containing these elements; an NHR-6 reporter fusion is expressed primarily in the anterior and posterior spermatheca during L3 and L4 larval stages, with some weak and variable expression also observed in two chemosensory neurons; NHR-6::GFP localizes to the nucleus; nhr-6 mRNA is expressed in an oscillating manner throughout larval development, in a pattern that is slightly irregular with respect to the timing of larval molts and that exhibits consistently lower expression at the times when these molts actually occur.
• Organism: Caenorhabditis elegans
• Automated Description: Enables DNA-binding transcription factor activity and sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II; regulation of ovulation; and spermathecum morphogenesis. Located in nucleus. Expressed in BAGL; BAGR; chemosensory neurons; head neurons; and spermatheca. Human ortholog(s) of this gene implicated in Parkinson's disease and extraskeletal myxoid chondrosarcoma. Is an ortholog of human NR4A2 (nuclear receptor subfamily 4 group A member 2) and NR4A3 (nuclear receptor subfamily 4 group A member 3).
• Biotype: SO:0001217
• Genetic Position: III :-5.49208 ±0.12253
• Length (nt): 5191

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00003605

Genomics

3 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:C48D5.1a.1	C48D5.1a.1	2359	III: 3573581-3578771
Transcript:C48D5.1b.1	C48D5.1b.1	1825	III: 3573851-3578390
Transcript:C48D5.1b.2	C48D5.1b.2	2062	III: 3576060-3578754

Other

2 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:C48D5.1a	C48D5.1a	1860	III: 3573699-3573740
CDS:C48D5.1b	C48D5.1b	1452	III: 3576353-3576468

23 RNAi Result

• WBRNAi00067025
• WBRNAi00042734
• WBRNAi00064804
• WBRNAi00064841
• WBRNAi00068806
• WBRNAi00012102
• WBRNAi00076224
• WBRNAi00063660
• WBRNAi00063661
• WBRNAi00072186
• WBRNAi00006029
• WBRNAi00027856
• WBRNAi00068744
• WBRNAi00107540
• WBRNAi00072185
• WBRNAi00064584
• WBRNAi00106637
• WBRNAi00111913
• WBRNAi00107442
• WBRNAi00063682
• WBRNAi00063687
• WBRNAi00107363
• WBRNAi00106714

94 Allele

• gk962532
• gk963881
• gk963882
• WBVar01262076
• WBVar01262085
• WBVar01262086
• tm870
• WBVar01656208
• WBVar01656209
• WBVar01656211
• WBVar01656210
• h17586
• h13727
• WBVar00045946
• WBVar00045951
• WBVar02034080
• WBVar00236291
• WBVar00056961
• gk171088
• gk171087
• WBVar00045956
• gk171090
• WBVar01408348
• gk171089
• WBVar00056966
• gk171084
• gk171086
• gk171085
• gk807015
• gk818026

1 Chromosome

• WormBase ID: III
• Organism: Caenorhabditis elegans
• Length (nt): 13783801

1 Chromosome Location

• Feature . Primary Identifier: WBGene00003605
• Start: 3573581
• End: 3578771
• Strand: 1

4 Data Sets

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

0 Downstream Intergenic Region

219 Expression Clusters

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Transcripts that showed significantly increased expression in L1 neural cells comparing to in adult neural cells.	DESeq2 (v1.18.1) fold change > 2, P-adj<0.05, using BenjaminiHochberg correction.	WBPaper00060811:L1_vs_adult_upregulated_neural
	Transcripts of coding genes that showed significantly decreased 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_depleted_coding-RNA
	Transcripts expressed in neuronal cells, by analyzingfluorescence-activated cell sorted (FACS) neurons.	DESeq. False discovry rate (FDR) < 0.1.	WBPaper00048988:neuron_expressed
	mRNAs that showed decreased expression in 1 cell mebryo comparing to in oocyte, according to RNAseq analysis.	Gaussian error propagation. As cutoff for the up-regulated genes authors used log2 fold change > 1 and P < 0.05 and as cutoff for the down-regulated genes authors used log2 fold change < -1 and P < 0.05.	WBPaper00045420:fertilization_downregulated_transcript
	Neuronally enriched transcripts according to a comparison of neuronal nuclei IP samples to total nuclei using isolation of nuclei from tagged specific cell types (INTACT) technology.	DESEQ2, fold change > 2 and FDR < 0.01.	WBPaper00062103:neuron_enriched
Bacteria: E.faecalis strain OG1RF	Transcripts that showed significantly increased expression after infection by E. faecalis OG1RF.	Ballgown was used to calculate differential expression of genes using FPKM data and to generate tables with fold change and P values. Genes were shortlisted with a cutoff of 2-fold change and P values of less than 0.05.	WBPaper00059754:E.faecalis_OG1RF_upregulated
Bacteria infection: Enterococcus faecalis	Genes with increased expression after 24 hours of infection by E.faecalis 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:E.faecalis_24hr_upregulated_TilingArray
	Transcripts that showed significantly increased expression after animals were treated with 100uM Rapamycin and 50mM Metformin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rapamycin-Metformin_upregulated
	Transcripts expressed in body muscle, according to PAT-Seq analysis using Pmyo-3-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:body-muscle_expressed
	Transcripts expressed in intestine, according to PAT-Seq analysis using Pges-1-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:intestine_expressed
	Transcripts that showed significantly increased expression in aak-1(tm1944);aak-2(ok524) animals comparing to in N2.	DEseq 1.18.0, adjusted p-value < 0.05.	WBPaper00056471:aak-1(tm1944);aak-2(ok524)_upregulated
Bacteria infection: Staphylococcus aureus MW2. 4 hours of exposure.	Transcripts that showed significantly increased expression after N2 animals had 4 hours of infection by Staphylococcus aureus (MW2).	DEseq 1.18.0, adjusted p-value < 0.05.	WBPaper00056471:S.aureus-4h_upregulated_N2
	Transcripts that showed significantly increased expression in nhr-114(gk849) comparing to wild type animals at L4 larva.	DESeq2 1.26.0, fold change > 2, FDR < 0.05.	WBPaper00064539:nhr-114(gk849)_upregulated
	Transcripts that showed significantly changed expression in 6-day post-L4 adult hermaphrodite comparing to in 1-day post L4 adult hermaphrodite animals.	Sleuth	WBPaper00051558:aging_regulated
	Transcripts that showed significantly increased expression in animal with pgph-2 overepxreesion [pgph-2p-pgph-2; myo-2p-mcherry] in glucose excess condition.	Genes with anadjusted P-value <= 0.05 found by DESeq2 were assigned as differentially expressed.	WBPaper00065926:pgph-2(overepxreesion)_upregulated_glucose
	Transcripts that showed significantly decreased exression in animals exposed to 100uM cadmium for 24 hours.	DESeq2 v1.20.0, fold change > 2, FDR < 0.05.	WBPaper00065029:cadmium_downregulated
	Transcripts that showed significantly increased expression in cco-1(RNAi) comparing to in vector control animals.	The limma package47 was used for differential expression. Genes with a Benjamini-Hochberg adjusted P-value <0.05 and an absolute log fold change of 2 were considered differentially expressed.	WBPaper00053402:cco-1(RNAi)_upregulated
	Transcripts that showed significantly increased expression in his-3(RNAi) comparing to in vector control animals.	The limma package47 was used for differential expression. Genes with a Benjamini-Hochberg adjusted P-value <0.05 and an absolute log fold change of 2 were considered differentially expressed.	WBPaper00053402:his-3(RNAi)_upregulated
	Transcripts that showed significantly increased expression in sftb-1(cer6) deletion homozygous comparing to to in N2 animals at L4 larva stage.	DESeq2, fold change > 2	WBPaper00058725:sftb-1(cer6)_downregulated
	Transcripts that showed significantly increased expression in xrep-4(lax137).	DESeq2. Genes were selected if their p value < 0.01.	WBPaper00066062:xrep-4(lax137)_upregulated
Reduced humidity (98% relative humidity).	Genes that were down-regulated after one day exposure to reduced humidity (98% relative humidity) according to microarray analysis.	Multiple hypothesis testing with the Benjamini-Hochberg correction was applied on calculated p-values. A change in the expression level was considered to be significant if the adjusted p-value was less than 0.001.	WBPaper00044578:reduced-humidity_downregulated_microarray
	Genes that showed oscillating mRNA expression level throughout the 16 hour time courses from L3 larva to young adult.	The following three lines of R code were used to perform the classification: increasing <-2*amplitude-PC1 < -1.7; oscillating <-!increasing & (amplitude > 0.55); flat <-!increasing & !oscillating; Note that the amplitude of a sinusoidal wave corresponds to only half the fold change between trough and peak.	WBPaper00044736:oscillating_dev_expression
	Transcripts that showed significantly increased expression in nuo-6(qm200) comparing to in N2.	Differential gene expression analysis was performed using the quasi-likeli-hood framework in edgeR package v. 3.20.1 in R v. 3.4.1.	WBPaper00053810:nuo-6(qm200)_upregulated
	Transcripts that showed significantly increased expression in hda-1(ne4752[3xFLAG-Degron-HDA-1]) in gonads dissected from 1-day old adult animals.	Salmon was used to map the mRNA-seq reads with the worm database WS268, and its output files were imported to DESeq2 in R. The differentially expressed genes were filtered by fold change more than 2 and adjusted p-value < 0.05. The scatter plots were generated by the plot function in R.	WBPaper00061479:hda-1(ne4752)_upregulated
	Transcripts that showed significantly increased expression in mep-1(ne4629[MEP-1-GFP-Degron]) in gonads dissected from 1-day old adult animals.	Salmon was used to map the mRNA-seq reads with the worm database WS268, and its output files were imported to DESeq2 in R. The differentially expressed genes were filtered by fold change more than 2 and adjusted p-value < 0.05. The scatter plots were generated by the plot function in R.	WBPaper00061479:mep-1(ne4629)_upregulated
	Transcripts that showed significantly increased expression in ubc-9(ne4833[ubc-9(G56R)] in gonads dissected from 1-day old adult animals.	Salmon was used to map the mRNA-seq reads with the worm database WS268, and its output files were imported to DESeq2 in R. The differentially expressed genes were filtered by fold change more than 2 and adjusted p-value < 0.05. The scatter plots were generated by the plot function in R.	WBPaper00061479:ubc-9(ne4833)_upregulated
	Transcripts that showed significantly increased expression in ngn-1(ok2200) embryos comparing to in N2.	DESeq2 ver.3.4.1	WBPaper00059537:ngn-1(ok2200)_upregulated
	Transcripts that showed significantly increased 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)_upregulated
	Transcripts that showed significantly decreased expression in eat-2(ad1116) comparing to in N2 at 3-days post L4 adult hermaphrodite animals.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:eat-2(ad1116)_downregulated
	Transcripts that showed significantly altered expression in rnp-6(dh1127) animals comparing to in N2 when fed with heat killed E. coli OP50.	Differentially expressed genes (DEGs) (q-value <0.05) between different samples were identified using the stringtie version 1.3.0, followed by Cufflinks version 2.2.	WBPaper00059824:rnp-6(dh1127)_regulated_OP50

10 Expression Patterns

• Primary Identifier: Expr2871
• Pattern: The mRNAs for lin-42, nhr-23, and nhr-41a exhibit a low-high (peak)-low profile during the L1 intermolt that is precisely reiterated at later stages. The mRNAs for nhr-25a, nhr-25b, and nhr-41b have a high-low-high (peak) expression profile during the L1 stage (and into early L2) that is also reiterated. nhr-25a and nhr-41b also show a downward trend in baseline expression as development proceeds. For all six mRNAs, there are peaks of expression that occur at precise intervals relative to the molt at all larval stages: nhr-25b and nhr-41b peak at the beginning of the intermolt; nhr-23 peaks at mid-intermolt, slightly preceding the intermolt peak in lin-42 expression; and nhr-25a and nhr-41a peak at the time the larval molts occur. Two mRNAs, nhr-6 and nhr-85a, show a more irregular expression pattern with respect to the molt; however, it should be noted that nhr-6 mRNA has consistent relatively lower expression values at the times the molt takes place. nhr-67 also does not display a reiterated, oscillating expression pattern, although two early peaks are observed at the end of the L1 stage and at the beginning of L2.

• Primary Identifier: Expr1031654
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr15973
• Pattern: A fosmid-based nhr-6::gfp reporter transgene revealed that nhr-6 was expressed in the nuclei of a small number of head neurons, including the BAGs.

• Primary Identifier: Expr2862
• Remark: Reporter gene fusion type not specified.
• Pattern: Expression of the nhr-6DGFP reporter was limited; robust expression was only observed in the posterior and anterior spermatheca during the L3 and L4 stages. Weak expression in two chemosensory neurons was variably observed at all stages.

• Primary Identifier: Expr1200175
• Pattern: Data from the TransgeneOme project

• Primary Identifier: Expr1582
• Remark: C48D5.1 = CNR8 in this article.
• Pattern: CNR8 showed greatest expression in L3, weak bands were also detected in L4 and adults after long time exposure. Only a single band of 3.1 kb was detected, except in L4 stage a 2.1 kb band is visible.

• Primary Identifier: Expr1011672
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr2014221
• 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: Expr2032462
• 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: Expr1146726
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

21 GO Annotation

13 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00003605
• Start: 3573581
• End: 3578771
• Strand: 1

21 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 5191

1 Sequence Ontology Term