WormMine: Gene WBGene00003156

• WormBase Gene ID: WBGene00003156
• Gene Name: mcm-4
• Sequence Name: Y39G10AR.14
• Brief Description: mcm-4 encodes a member of the MCM2/3/5 family with similarity to human MCM4 minichromosome maintenance deficient 4 protein, and affects embryonic viability, nuclear morphology in early embryos, and larval viability.
• Organism: Caenorhabditis elegans
• Automated Description: Predicted to enable single-stranded DNA binding activity. Predicted to contribute to single-stranded DNA helicase activity. Involved in gonad development; locomotion; and nervous system development. Located in nucleus. Expressed in several structures, including P lineage cell; Q lineage cell; Z2; Z3; and somatic gonad precursor. Human ortholog(s) of this gene implicated in immunodeficiency 54. Is an ortholog of human MCM4 (minichromosome maintenance complex component 4).
• Biotype: SO:0001217
• Genetic Position: I :-9.34989 ±0.051559
• Length (nt): 3527

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00003156

Genomics

2 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:Y39G10AR.14a.1	Y39G10AR.14a.1	2615	I: 2318291-2321817
Transcript:Y39G10AR.14b.1	Y39G10AR.14b.1	225	I: 2318427-2318651

Other

2 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:Y39G10AR.14b	Y39G10AR.14b	225	I: 2318427-2318651
CDS:Y39G10AR.14a	Y39G10AR.14a	2472	I: 2318427-2318730

18 RNAi Result

• WBRNAi00099829
• WBRNAi00100494
• WBRNAi00087691
• WBRNAi00100868
• WBRNAi00099223
• WBRNAi00099627
• WBRNAi00099425
• WBRNAi00100681
• WBRNAi00081345
• WBRNAi00056267
• WBRNAi00100307
• WBRNAi00116625
• WBRNAi00026670
• WBRNAi00026671
• WBRNAi00100120
• WBRNAi00000124
• WBRNAi00101055
• WBRNAi00075572

65 Allele

• gk963902
• gk964159
• otn10613
• gk963630
• WBVar01694604
• WBVar01694603
• WBVar01430582
• gk311703
• gk780194
• gk732741
• gk441286
• gk916123
• gk104899
• gk885195
• gk104900
• gk477392
• gk768414
• gk359454
• gk588502
• gk479710
• gk485407
• gk799000
• gk692186
• gk811366
• gk395709
• WBVar01331649
• WBVar01279300
• gk352257
• gk533086
• e1466

1 Chromosome

• WormBase ID: I
• Organism: Caenorhabditis elegans
• Length (nt): 15072434

1 Chromosome Location

• Feature . Primary Identifier: WBGene00003156
• Start: 2318291
• End: 2321817
• 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

235 Expression Clusters

Regulated By Treatment	Description	Algorithm	Primary Identifier
	oocyte proteins identified by two or more unique peptides during proteomics study.	In the pooled data set, 1453 C. elegans proteins were identified with a probability >= 0.9 according to ProteinProphet, of which 1165 proteins were identified by more than one unique peptide.	WBPaper00038289:oocyte_protein
	Genes with expression altered >= 3-fold in dpy-10(e128) mutants.	Data across the wild type series was analyzed using the Significance analysis of Microarrays (SAM) algorithm (to calculate the False Discovery Rate (FDR)).	WBPaper00035873:dpy-10_regulated
	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
adult vs dauer larva	Transcripts that showed differential expression in adult vs dauer lava in N2 animals at 20C.	N.A.	WBPaper00050488:adult_vs_dauer_regulated_N2_20C
	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
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
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
	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 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
	Proteins interacting with NHR-49-GFP according to co-IP and LC-MS.	N.A.	WBPaper00064071:NHR-49_interacting
	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 GABAergic neuron, according to PAT-Seq analysis using Punc-47-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:GABAergic-neuron_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 expressed in NMDA neuron, according to PAT-Seq analysis using Pnmr-1-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:NMDA-neuron_expressed
	Transcripts expressed in pharynx, according to PAT-Seq analysis using Pmyo-2-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:pharynx_expressed
	Transcripts expressed in seam cells, according to PAT-Seq analysis using Pgrd-10-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:seam_expressed
	Transcripts that showed significantly decreased expression in day 3 adult hermaphrodite comparing to in L4 larva daf-16(mu86);glp-1(e2141) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-3-adult_vs_L4_downregulated_daf-16(mu86);glp-1(e2141)
	Transcripts that showed significantly decreased expression in day 3 adult hermaphrodite comparing to in L4 larva glp-1(e2141) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-3-adult_vs_L4_downregulated_glp-1(e2141)
	Transcripts that showed significantly increased expression in day 3 adult hermaphrodite comparing to in L4 larva fem-3(q20) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-3-adult_vs_L4_upregulated_fem-3(q20)
Bacteria diet: Escherichia coli HB101. Fed for 30 generations.	Transcripts that showed significantly decreased expression after fed by bacteria E. coli HB101 for 30 generations comparing to animals fed by E. coli OP50.	DESeq2 fold change > 2, p-value < 0.01.	WBPaper00061007:HB101_downregulated
Bacteria diet: Sphingomonas aquatilis Yellow. Fed for 30 generations.	Transcripts that showed significantly decreased expression after fed by bacteria Sphingomonas aquatilis (Yellow) for 30 generations comparing to animals fed by E. coli OP50.	DESeq2 fold change > 2, p-value < 0.01.	WBPaper00061007:S.aquatilis_downregulated
Bacteria infection: Bacillus thuringiensis	mRNAs that showed significantly decreased expression after pathogenic bacteria Bacillus thuringiensis infections comparing to non pathogenic BT (BT247(1 to 10 mix) vs BT407 12h), according to RNAseq.	Cuffdiff, ajusted p-value < 0.01.	WBPaper00046497:B.thuringiensis_0.1mix_downregulated_12h
Bacteria infection: Bacillus thuringiensis	mRNAs that showed significantly decreased expression after pathogenic bacteria Bacillus thuringiensis infections comparing to non pathogenic BT (BT247(1 to 2 mix) vs BT407 12h), according to RNAseq.	Cuffdiff, ajusted p-value < 0.01.	WBPaper00046497:B.thuringiensis_0.5mix_downregulated_12h
	Maternal class (M): genes that are called present in at least one of the three PC6 replicates.	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_M
	mRNAs that showed differential expression in activated AAK-2(uthIs202[aak-2 (intron 1)::aak-2(aa1-aa321)::Tomato::unc-54 3'UTR + rol-6(su1006)]), activiated CRTC-1 (uthEx222[crtc-1p::crtc-1 cDNA (S76S, S179A)::tdTomato::unc-54 3'UTR + rol-6(su1006)]), or AAK-2;CRTC-1 comparing to in N2.	Genes were tested for differential expression between each mutant strain and wild-type using edgeRs glm method. Briefly, negative binomial models were fitted and dispersion estimates obtained. These were then used to calculate average levels of change between conditions and determine differential expression, using the generalized linear model likelihood ratio test. For each comparison, genes with less than 5 CPM were filtered and those with at least 50% change and False Discovery Rate (FDR) of 1% or less were considered differentially expressed.	WBPaper00046499:AMPK_regulated
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 animals exposed to 400uM tamoxifen from L1 to L4 larva stage.	DEseq2, fold change > 2	WBPaper00064505:tamoxifen_upregulated
	Top 300 transcripts enriched in ABalppppppa, ABpraaapppa 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:ASE_parent
	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

6 Expression Patterns

• Primary Identifier: Expr1031491
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr11524
• Remark: Temporal description
• Subcellular Localization: By antibody staining, MCM-4 was found to be expressed in dividing cells during all stages of development in wild-type animals. Embryos showed the highest levels of MCM-4 expression, in agreement with the fact that more than half of the somatic cells are formed during embryogenesis. Even dauer larvae that had been arrested in cell division for 2 weeks still contained detectable MCM-4 protein levels. These results suggest that a pool of MCM-4 is retained during prolonged periods of quiescence, so that MCM-4 might function in the re-initiation of DNA synthesis when conditions improve. Immunostaining of wild-type animals for MCM-4 showed strong nuclear staining in the gonad, embryos and postembryonic lineages. MCM-4 was detectable in sperm and accumulated during oocyte maturation in the nucleus but did not show overlap with the condensed chromosomes in diakinesis of meiotic prophase. MCM-4 was not chromatin-associated during MeiosisI of the fertilized oocyte, and the first polar body did not contain MCM-4. This finding is consistent with the absence of S phase between Meiosis I and -II. The second polar body and maternal pronucleus received some MCM-4. Subsequently, embryonic cells in interphase showed strong nuclear staining. In prophase, MCM-4 localization did not overlap with the condensing chromosomes. Upon nuclear envelope degradation, MCM-4 became diffusely localized throughout the cell and clearly did not co-localize with the metaphase-aligned chromosomes. MCM-4 remained cytoplasmic at the onset of anaphase; however, chromatin association became apparent in late anaphase. These data show that chromosome association of MCM-4 is tightly controlled, consistent with origin licensing taking place at the end of mitosis and disappearing during S phase. Similar observations were made during larval divisions. Matching the MCM-4::mCherry reporter, endogenous MCM-4 expression was detectable prior to and during mitosis. Staining of synchronized L1 animals revealed the timing of MCM-4 expression, which in general preceded mitosis by 1-2 h. After 5 h of L1 development at 20 C, MCM-4 immunostaining was predominantly detected in the epithelial seam cells, Q neuroblast daughters and gonad primordium. The somatic gonad precursor cells Z1 and Z4 showed nuclear staining, while the mitotically arrested germline precursor cells Z2 and Z3 showed diffuse cytoplasmic staining. At 6 hours of L1 development, the mesoblast (M) also stained strongly as well as the most anterior ventral cord precursors cells (W, P1 and P2). Subsequently at 7 h, additional P cells showed nuclear MCM-4 expression, which became apparent prior to migration of the nucleus into the ventral nerve cord. At 8 h of L1 development, the intestinal nuclei showed MCM-4 expression, which preceded nuclear division by at least 4 h. At subsequent time points, daughter cells that continued division, such as the Pn.a and M descendants, retained strong nuclear staining. L2 animals stained at 16 h of larval development showed strong MCM-4 expression in the gonad, the H1.a, H2.p, V1-6.p and T.ap seam cells and, weakly, the intestinal nuclei (data not shown). Importantly, MCM-4 staining did not overlap with DNA in prophase and metaphase, while in late anaphase co-localization with the chromosomes was clearly detectable. Similar to our observations with the MCM-4::mCherry reporter, we could not detect any asymmetry in MCM-4 segregation. Thus, even if only one daughter cell continued cell division, both daughters received a similar amount of MCM-4in mitosis. Furthermore, the MCM-4protein became undetectable during quiescence, i.e. the P3.p-P8.p daughter cells that resume DNA replication in the L3 stage did not show detectable expression in the L2 stage. Altogether, our reporter gene and antibody staining analysis show that MCM-4 is dynamically expressed and localized during larval development as well as during different phases of the cell cycle. Expression of MCM-4::mCherry was specifically induced in all postembryonic blast cell lineages well before mitotic entry, at the expected time of S-phase induction. The fusion protein localized to the cell nucleus until degradation of the nuclear envelope in prometaphase, at which point MCM-4 became diffusely localized through the cell. This diffuse localization indicates that MCM-4 is not chromatin-associated in mitosis. MCM-4::mCherry did not disappear upon completion of mitosis but was segregated to both daughter cells. Even cells that permanently withdrew from cell division, such as the motor neurons of the ventral nerve cord, initially retained MCM-4::mCherry expression. However, this expression subsequently disappeared in differentiated cells as well as in cells that temporarily arrested cell division, such as the Pn.p vulval precursor cells in the ventral cord. These experiments indicate that mcm-4 is transcriptionally activated at approximately the time of G1/S transition and that MCM-4 protein is segregated to both daughter cells in mitosis.

• Primary Identifier: Expr2013451
• 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: Expr1159749
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr1026883
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr2031685
• 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).

35 GO Annotation

10 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00003156
• Start: 2318291
• End: 2321817
• Strand: -1

35 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 3527

1 Sequence Ontology Term

• Name: gene

5 Strains

• WBStrain00022586
• WBStrain00022592
• WBStrain00023671
• WBStrain00026847
• WBStrain00004489

1 Upstream Intergenic Region

• WormBase ID: intergenic_region_chrI_2321818..2322024
• Length (nt): 207
• Chromosome Location: I: 2321818-2322024
• Organism: Caenorhabditis elegans