WormMine: Gene WBGene00003377

• WormBase Gene ID: WBGene00003377
• Gene Name: mls-2
• Sequence Name: C39E6.4
• Brief Description: mls-2 encodes a homeodomain protein of the HMX family; during postembryonic development, MLS-2 is required for cell proliferation, cleavage orientation, and fate specification in the mesodermal M lineage; in regulating M lineage proliferation and fate specification, MLS-2 appears to act upstream of CYE-1/cyclin E and HLH-1/CeMyoD, respectively, the latter of which is not expressed in the M lineage in mls-2 mutant animals; MLS-2 is expressed in the nuclei of early proliferating undifferentiated M lineage cells (up to the 8-M stage), in a subset of head neurons, and in cells near the vulva during the L2 and L3 larval stages.
• Organism: Caenorhabditis elegans
• Automated Description: Enables RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in several processes, including establishment of mitotic spindle orientation; neuron differentiation involved in amphid sensory organ development; and regulation of cell differentiation. Located in nucleus. Expressed in several structures, including AB lineage cell; AWC-ON; M.dla; head; and somatic nervous system. Human ortholog(s) of this gene implicated in oculoauricular syndrome. Is an ortholog of human HMX1 (H6 family homeobox 1).
• Biotype: SO:0001217
• Genetic Position: X :-6.69708 ±0.01114
• Length (nt): 2837

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00003377

Genomics

1 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:C39E6.4.1	C39E6.4.1	1323	X: 4758804-4761640

Other

1 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:C39E6.4	C39E6.4	1026	X: 4759073-4759235

8 RNAi Result

• WBRNAi00001129
• WBRNAi00042211
• WBRNAi00042212
• WBRNAi00011781
• WBRNAi00011782
• WBRNAi00029684
• WBRNAi00061153
• WBRNAi00061154

64 Allele

• gk964260
• gk962667
• gk963869
• gk963870
• WBVar01601660
• gk912513
• gk618729
• WBVar00078212
• WBVar01710800
• WBVar01710797
• WBVar01710799
• WBVar01710798
• tm252
• ns158
• ns156
• ns159
• gk278882
• gk278881
• gk278880
• gk278879
• gk278878
• gk278877
• gk278876
• gk278875
• gk278885
• gk278884
• gk278883
• cc615
• WBVar02015533
• WBVar02015534

1 Chromosome

• WormBase ID: X
• Organism: Caenorhabditis elegans
• Length (nt): 17718942

1 Chromosome Location

• Feature . Primary Identifier: WBGene00003377
• Start: 4758804
• End: 4761640
• 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_chrX_4757198..4758803
• Length (nt): 1606
• Chromosome Location: X: 4757198-4758803
• Organism: Caenorhabditis elegans

148 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
Osmotic stress	Transcripts that showed significantly altered expression with 500 mM salt (NaCl) vs 100 mM salt when food was present	DESeq(version 1.10.1), FDR < 0.05.	WBPaper00050726:OsmoticStress_regulated_Food
	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
Osmotic stress	Transcripts that showed significantly altered expression with 500 mM salt (NaCl) vs 100 mM salt when no food was present	DESeq(version 1.10.1), FDR < 0.05.	WBPaper00050726:OsmoticStress_regulated_NoFood
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 50uM Rifampicin and 250uM Allantoin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rifampicin-Allantoin_upregulated
	Transcripts that showed significantly increased expression after animals were treated with 50uM Rifampicin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rifampicin_upregulated
	Transcripts that showed significantly increased expression after animals were treated with 100uM Psora and 250uM Allantoin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Psora-Allantoin_upregulated
	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 that showed significantly decreased expression in lipl-4 overexpression transgenic lines comparing to wild type control animals.	DESeq2 fold change > 2, FDR < 0.05.	WBPaper00064156:lipl-4(overexpress)_downregulated
	Transcripts that showed significantly increased expression in sin-3(tm1276) comparing to in N2.	DESeq2, fold change > 2, p-value < 0.01.	WBPaper00061203:sin-3(tm1276)_upregulated
	Transcripts that showed significantly decreased 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)_downregulated
	Transcripts that showed significantly increased expression after exposure to 75uM paraquat(PQ) from L1 to day 2 adult stage in skn-1(lax188) animals	fold change > 2	WBPaper00058711:paraquat_upregulated
25C vs. 20C	Transcripts that showed significantly increased expression in 1-day post L4 adult hermaphrodite N2 grown at 25C, comparing to in N2 animals grown at 20C.	CuffDiff, fold change > 2.	WBPaper00065096:25C_vs_20C_upregulated
	Transcripts that showed significantly increased expression in 10-days post L4 adult hermaphrodite N2 grown at 20C, comparing to in 1-day post L4 adult hermaphrodite N2 animals grown at 20C.	CuffDiff, fold change > 2.	WBPaper00065096:Day10_vs_Day1_upregulated
	Transcripts that showed significantly increased expression in wdr-5(ok1417);skn-1(lax188) comparing to in skn-1(lax188) at day 2 adult stage.	fold change > 2	WBPaper00058711:wdr-5(ok1417)_upregulated
	Transcripts that showed significantly decreased expression in 10-days post L4 adult hermaphrodite npr-8(ok1439) animals grown at 20C, comparing to in N2 animals.	CuffDiff, fold change > 2.	WBPaper00065096:npr-8(ok1439)_downregulated_Day10_20C
	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 ilc-17.1(syb5296) comparing to in N2 animals at L4 larva stage.	DESeq2, fold change > 2, FDR < 0.05.	WBPaper00066594:ilc-17.1(syb5296)_upregulated
Bacteria infection: Pseudomonas aeruginosa PA14. 4 hours at 25C.	Transcripts that showed significantly decreased expression after N2 L4 animals were infected by P. aeruginosa (PA14) bacteria for 24 hours at 25C.	DESeq R package (1.18.0), FDR < 0.05 and fold change > 2.	WBPaper00062184:PA14_downregulated
	Transcripts that showed significantly decreased 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)_downregulated
	Transcripts that showed significantly decreased expression in nhl-2(ok818) comparing to in N2 at 25C.	EdgeR, FDR < 0.05, fold change < 0.5.	WBPaper00055971:nhl-2(ok818)_25C_upregulated
	Transcripts that showed significantly increased expression in animals lacking P granules by RNAi experiments targeting pgl-1, pgl-3, glh-1 and glh-4, and unc-119-GFP(+), comparing to in control animals, at 2-day post L4 adult hermaphrodite stage.	DESeq2, Benjamini-Hochberg multiple hypothesis corrected p-value < 0.05 and fold change > 2.	WBPaper00050859:upregulated_P-granule(-)GFP(+)_vs_control_day2-adult
	Genes expressed in N2.	Expressed transcripts were identified on the basis of a Present call in 3 out of 4 N2 experiments as determined by Affymetrix MAS 5.0.	WBPaper00025141:N2_Expressed_Genes
	Genes upregulated in dcr-1(-/-) adult animals by at least 1.5 fold and P < 0.01, as determined by a multisample t-test and the Benjamini and Hochberg false discovery rate correction.	Statistical t-test: P < 0.05 for rde-4(-/-) and rde-1(-/-) analyses; P < 0.01 for dcr-1(-/-) analysis with a threshold of 1.5-fold misregulation.	WBPaper00029437:dcr-1_upregulated
	Transcripts that showed significantly increased expression in animals fed with JM103 bacteria producing Cry5B, comparing to control animals fed with JM103.	ANOVA, p-value < 0.05.	WBPaper00056167:Cry5B_upregulated
	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
	Transcripts that showed significantly increased expression in spr-1(ok2144) comparing to in N2.	DESeq2, fold change > 2, p-value < 0.01.	WBPaper00061203:spr-1(ok2144)_upregulated

13 Expression Patterns

• Primary Identifier: Expr1031555
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr7471
• Remark: Clone: pUL#JRH10G4
• Pattern: Expression observed from early embryo to adult. Early and mid embryo show expression in several cells. Strongest expression is in late embryos and L1 in dorsal and ventral nerve cords and three pairs of head nerves, one pair with processes to head tip. After L1 dorsal nerve cord and one pair of head nerves show expression. Weak expression seen in two pairs of tail nerves. Expression sometimes seen in structures at head tip (possibly the arcade cells or head hypodermis). Possibly artifactual expression seen in body wall muscles, head muscles and intestine.

• Primary Identifier: Expr12839
• Pattern: mls-2 expression was observed in the AWC neurons in L1 larvae shortly after hatching. mls-2 is not expressed in the AWC neurons in adult animals.

• Primary Identifier: Expr15631

• Primary Identifier: Expr8055
• Remark: Picture: Figure 1.
• Pattern: During postembryonic development, GFP was observed in several cell types. At the L1 stage, GFP was transiently expressed in the early M lineage. During the L2 and L3 stages, GFP was transiently detected in a group of proliferating cells surrounding the gonad, which are presumably somatic gonad cells from the Z lineage. GFP expression was also detected in three pairs of head neurons throughout postembryonic development. Two pairs of the neurons, AIM and ASK, express mls-2 (based on their location, their axon structures, co-localization with a ttx-3::rfp (an AIY specific marker) and DiO staining which stains amphid and phasmid neurons in the head and tail).

• Primary Identifier: Expr15952
• Pattern: The mNG::SEC::mls-2 knock-in allele is a transcriptional reporter of mls-2, since the self-excising cassette (SEC) contains transcriptional terminators. mNG::SEC::mls-2 knock-in showed diffuse mNG expression in numerous cells in the head and the M mesoblast of first-stage larvae.

• Primary Identifier: Expr15953
• Pattern: mNG::mls-2 knock-in animals displayed wild-type AWC asymmetry as determined by the expression of the AWCON marker str-2p::TagRFP, suggesting that mNG::MLS-2 fusion protein is functional in AWC development. Like GFP::MLS-2 expressed from transgenes, mNG::MLS-2 knock-in was localized in the nucleus of AWC precursor cells in early embryos but was not observed in AWC cells in late embryos or early-stage larvae. Similar to MLS-2 antibody staining and GFP::MLS-2 transgenes (Jiang et al., 2005), mNG::MLS-2 knock-in was localized to the nucleus of a subset of head cells and the M mesoblast in first-stage larvae and adults.

• Primary Identifier: Expr16132
• Pattern: GFP::MLS-2 expression became detectable around the 50-cell stage of embryogenesis and was restricted to specific, reproducible sublineages of the AB blastomere, most of which gave rise to neuronal and/or glial descendants. GFP::MLS-2 was also expressed in the duct and pore lineages, but was never observed in the canal cell. In 3/3 movies, we saw that expression of GFP::MLS-2 initiated in the grandparents of the duct and pore cell. GFP::MLS- 2 expression persisted in the duct and pore cells through the ventral enclosure and 1.5-fold stages of embryonic development, during which time fates are specified via EGF-Ras- ERK signaling and the duct and pore cells stack and form tubes (Abdus-Saboor et al., 2011). By the first larval stage of development, when the duct and pore cells have achieved their mature morphologies, GFP::MLS-2 was no longer detected in the duct and pore cells.

• Primary Identifier: Expr3651
• Pattern: The GFP::MLS-2 fusion construct and antibody staining showed identical expression patterns. Expression of MLS-2 was first detectable in one or two cells in embryos at the 50-cell stage and is localized in the nucleus. MLS-2 continued to be expressed in proliferating cells that are primarily located at the anterior of the embryo and are presumably derived from the AB lineage. During morphogenesis, this expression became restricted to a small subset of head neuronal precursors. Expression persisted in six head neurons during postembryonic development. GFP::MLS-2 expression was also observed in unidentified cells near the vulva at the L2 and L3 stages. To characterize the M lineage expression pattern of mls-2, double-labeling experiments were performed using anti-MLS-2 antibodies and the M lineage-specific hlh-8::gfp or hlh-8::lacZ markers. mls-2 expression in the M lineage was first detectable in the M mesoblast, and was retained during the first three rounds of cell divisions, such that mls-2 expression was still detectable in eight M descendants (designated 8-M stage, n>200). However, after one more round of cell division (at the 16-M stage), no MLS-2 signal was detected either by anti-MLS-2 antibodies or by the gfp::mls-2 fusion construct. Although it is possible that a low level of MLS-2 protein is present after the 8-M stage, the loss of MLS-2 signal at the 16-M stage appears to be due to the instability of the MLS-2 protein, because the mls-2 promoter is still active in M lineage descendants after the fourth round of cell division, as detected by a transcriptional mls-2p::gfp::mls-2 3' UTR construct. Neither the mls-2 promoter activity nor the MLS-2 protein was detected in the SM lineage or the differentiated BWMs and CCs. Thus mls-2 is expressed in the proliferating cells of the early M lineage.
• Subcellular Localization: Localized in the nucleus.

• Primary Identifier: Expr2013602
• 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: Expr1027722
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr1146204
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr2031835
• 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).

18 GO Annotation

13 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00003377
• Start: 4758804
• End: 4761640
• Strand: -1

18 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 2837

1 Sequence Ontology Term