WormMine: Gene WBGene00000516

• WormBase Gene ID: WBGene00000516
• Gene Name: cki-1
• Sequence Name: T05A6.1
• Brief Description: cki-1 encodes a homolog of the mammalian cyclin-dependent kinase inhibitor p27/KIP1 that is required for the arrest of cell division in larval blast lineages, dauer larvae and starved L1 larvae; excess CKI-1 expression prematurely stops cell division while cki-1(RNAi) induces extra cell divisions, indicating that CKI-1 quantitatively regulates the amount of mitosis in postembryonic worms.
• Organism: Caenorhabditis elegans
• Automated Description: Predicted to enable cyclin-dependent protein serine/threonine kinase inhibitor activity. Involved in several processes, including gonad development; regulation of cell cycle process; and regulation of cell division. Located in nucleus. Expressed in several structures, including excretory duct; hermaphrodite somatic gonadal cell; hypodermal cell; pharynx; and somatic gonad precursor. Human ortholog(s) of this gene implicated in several diseases, including hematologic cancer (multiple); lung carcinoma (multiple); and urinary system cancer (multiple). Is an ortholog of human CDKN1B (cyclin dependent kinase inhibitor 1B).
• Biotype: SO:0001217
• Genetic Position: II :0.566619 ±0.001788
• Length (nt): 866

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00000516

Genomics

1 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:T05A6.1.1	T05A6.1.1	809	II: 7811240-7812105

Other

1 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:T05A6.1	T05A6.1	555	II: 7811259-7811467

52 RNAi Result

• WBRNAi00067518
• WBRNAi00064851
• WBRNAi00052441
• WBRNAi00074680
• WBRNAi00063066
• WBRNAi00064856
• WBRNAi00062688
• WBRNAi00074683
• WBRNAi00074686
• WBRNAi00074681
• WBRNAi00074682
• WBRNAi00074685
• WBRNAi00085317
• WBRNAi00085316
• WBRNAi00072618
• WBRNAi00018179
• WBRNAi00064853
• WBRNAi00063062
• WBRNAi00063065
• WBRNAi00077612
• WBRNAi00066481
• WBRNAi00063837
• WBRNAi00022986
• WBRNAi00086535
• WBRNAi00098884
• WBRNAi00077611
• WBRNAi00111684
• WBRNAi00035167
• WBRNAi00072619
• WBRNAi00072620

11 Allele

• gk963801
• gk963053
• gk962682
• gk941931
• gk132
• gk673821
• gk549685
• gk575569
• gk403392
• gk147665
• gk883742

1 Chromosome

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

1 Chromosome Location

• Feature . Primary Identifier: WBGene00000516
• Start: 7811240
• End: 7812105
• 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_7812106..7812602
• Length (nt): 497
• Chromosome Location: II: 7812106-7812602
• Organism: Caenorhabditis elegans

261 Expression Clusters

Regulated By Treatment	Description	Algorithm	Primary Identifier
	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 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
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 expressed in the epithelial tissues surrounding the pharynx that includes the arcade and intestinal valve (AIV) cells, according to PAT-Seq analysis using Pbath-15-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:arcade_intestinal-valve_expressed
	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 hypodermis, according to PAT-Seq analysis using Pdpy-7-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:hypodermis_expressed
	Transcripts expressed in intestine, according to PAT-Seq analysis using Pges-1-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:intestine_expressed
	Genes up regulated in alg-1(gk214) comparing to in N2.	Differential expression was assessed using an empirical Bayes statistics using the eBayes function.	WBPaper00040823:alg-1(gk214)_upregulated
	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 rrf-3(pk1426) comparing to in N2 at embryo stage.	DESeq2v 1.18.1, fold change > 1.5, adjusted p-value < 0.01.	WBPaper00056169:rrf-3(pk1426)_upregulated_embryo
	Transcripts that showed significantly increased expression after four-day-old young adult worms were placed on NGM plates seeded with OP50 in the presence 5% Agaro-oligosaccharides(AGO) for 24 h, comparing to animals grown in the absence of AGO.	Fold change > 2.	WBPaper00064306:Agaro-oligosaccharides_upregulated
	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
starvation 12 hours	Transcripts that showed significantly increased expression in dissected intestines of N2 L1 larva that were starved for 12 hours, comparing to fed animals.	EdgeR, FDR < 0.05, fold change >= 2.	WBPaper00067259:starvation_upregulated_intestine
	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
	Genes that showed significantly increased expression in daf-2(e1370) comparing to in N2.	To identify DEGs, Students t test and the log2 median ratio test were performed to compute t values and median ratios for all the annotated genes. The adjusted P values from each test were computed using an empirical distribution of the null hypothesis, which was obtained from random permutations of the samples. Finally, the adjusted P values from the individual tests were combined to compute the overall P values using Stouffers method , and genes with overall P < 0.05 and fold change > 1.5 were selected as DEGs.	WBPaper00047131:daf-2(e1370)_upregulated_N2-background
	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 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
	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
Gamma irradiation 100 mGY per hour for 72 hours since L1 larva.	Transcripts that showed significantly increased expression after exposure to 100mGy per hour gamma irradiation from L1 to day 1 adult hermaphrodite stage.	DESeq2, FDR <= 0.05, log2 fold change >= 0.3 or <= -0.3.	WBPaper00058958:100mGy-irradiation-72h_upregulated
	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
	Genes that showed expression levels higher than the corresponding reference sample (L2 all cell reference).	A Mann-Whitney U test with an empirical background model and FDR correction for multiple testing was used to detect expressed transcripts (Benjamini and Hochberg 1995). Genes and TARs with an FDR <= 0.05 were reported as expressed above background. Authors detected differentially expressed transcripts using a method based on linear models. Genes and TARs were called differentially expressed if the FDR was <= 0.05 and the fold change (FC) >= 2.0. To more strictly correct for potential false-positives resulting from multiple sample comparisons, authors divided individual FDR estimates by the number of samplesor sample comparisons, respectively. This resulted in an adjusted FDR of 1.3 * 0.0001 for expression above background and of 7.4 * 0.0001 for differential expression. Authors called genes selectively enriched in a given tissue if they met the following requirements: (1) enriched expression in a given tissue (FDR <= 0.05 and FC >= 2.0), (2) fold change versus reference among the upper 40% of the positive FC range observed for this gene across all tissues, and (3) fold-change entropy among the lower 40% of the distribution observed for all genes.	WBPaper00037950:coelomocytes_L2-larva_expressed
	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

13 Expression Patterns

• Primary Identifier: Expr4691
• Pattern: GFP was detected in epidermal cells including the head epidermal cells hyp1 to hyp5, the hyp7 syncytium, the tail epidermal cells hyp8 to hyp11, and the ventral Pn.p cells. GFP expression was also detected in the excretory duct cell.

• Primary Identifier: Expr4746
• Remark: Gene_regulation: The amount of anti-CKI-1 signal per distal nucleus in cul-2(ek1) gonads is 13-fold higher than in the wild type (13 plusminus 10 arbitrary units (a.u.), n = 50, versus 1.0 plusminus 0.9 a.u., n = 36).
• Pattern: In the distal mitotic germ cells of wild-type animals, the amount of CKI-1 is low. As germ cells enter meiosis, the level of CKI-1 increases, with the highest intensity being observed in oocyte nuclei.

• Primary Identifier: Expr4662
• Pattern: cki-1 expression, detected by a cki-1 promoter::GFP fusion gene, was much higher in the Z1.aa/Z4.pp cells than in the Z1.ap/Z4.pa cells.

• Primary Identifier: Expr1030306
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr2640
• Remark: Expression of reporters containing 2 or 6 kb of sequences upstream of the gene was not observed in the embryonic gut lineage. It has been shown that cell- or tissue-specific cis-regulatory elements of the Drosophila string/cdc25 gene, a developmentally controlled cell cycle regulator, extend over a 30 kb interval. Thus, it is conceivable that the spatiotemporal expression of cki-1 is also controlled by an extended stretch of cis-regulatory elements. The 20 kb region upstream of the cki-1 gene does not contain any predicted protein coding sequences and it is possible that a cis-acting element required for embryonic gut expression may reside 6kb upstream of the gene. Indeed, we found that when a cki-1 reporter gene was co-transformed with two cosmids containing ~30 kb of sequence upstream of the gene, the resultant extrachromosomal array, which is presumably generated by homologous recombination of the introduced DNA, expresses GFP in the gut cells at around the comma stage. However, the level of expression is too low and variable to identify in which gut cells GFP is expressed. Moreover, the cosmid T05A6, which contains about 11 kb upstream sequence of the cki-1 gene, can rescue the gut hyperplasia in mnDf100 embryos.
• Pattern: cki-1 reporter expression is first detectable in a group of cells of the pharynx and nervous system at about six hours post-fertilization. This represents the time at which most cells in the embryo become postmitotic. Following this initial burst of expression, reporter expression expands to include most of the anteriorly located cells.

• Primary Identifier: Expr608
• Remark: In the absence of food expression is very high in arrested larvae and then fades by 8-12h post-feeding. See Table 2 in the article cgc3201 for the stage/tissue type expression patterns of this locus. Lineage expression: SM lineage. This information was extracted from published material (Archana Sharma-Oates, Andrew Mounsey and Ian A. Hope).
• Pattern: First detected at comma stage in pharyngeal primordium as pharyngeal muscles begin terminal differentiation. Strong expression is detected in most cells during late embryogenesis when cells are either differentiating or undergoing cell cycle arrest prior to hatching. At hatching and in L1 animals maintained in absence of food expression detected in Q, M, Z1, Z4 and V cells. Expression in these cells fades after feeding when cell division resumes. Strong expression is observed in many postmitotic neurons and muscle cells. Stronger expression is detected in newly differentiated cells and then gradually decreases. cki-1 also expressed in dauer larvae. 1. Lateral hyodermal V lineage: V cells show strong expression until they divide in the mid L1 (fluorescence decreases significantly). Seam cells express at quite high levels during resting phases between molts and at a reduced level during division. Expression increases at L4 (coincident with seam cell terminal differentiation). 2. sex myoblasts (SM)lineage: High level of expression observed during SM migration, reduced during SM division and high again as the sex muscles differentiate. 3. P lineage: L1-molt progeny of Pn.a neuroblasts express high levels of cki-1::gfp. 4. Somatic gonad: Expression in Z1 and Z4 diminishes prior to cell division in mid-L1. Strong expression in Z1.aa and Z4.pp, the distal tip cells, beginning in L2, undetectable in the rest of Z1/Z4 lineage until the late L3 and early L4. Expression in somatic gonad increases dramatically at the onset of terminal differentiation. 5. Intestine: After L1-molt expression in intestine is seen throughout the larval stages 6. Vulva precursor cells: cki-1::gfp expression first detected in vulva precursor cells (VPCs) in late L1 or early L2 and peaks at L2 molt.

• Primary Identifier: Expr12576
• Pattern: Using single molecule fluorescent in situ hybridization (smFISH), high levels of transcript for cki-1 (Cip/Kip family CDK inhibitor), which promotes G1 arrest, were found in the anchor cell.

• Primary Identifier: Expr2010031
• 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: Expr2028272
• 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: Expr1156061
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr2998
• Subcellular Localization: Nuclear CKI-1-GFP was detected in the VPCs of wild-type animals during late L1, the time at which the decision to arrest divisions is made.

• Primary Identifier: Expr1026898
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr10546
• Subcellular Localization: In pat-3(+) rescued animals, the appearance of CKI-1::GFP is a distinct fluorescent spot within a round green nucleus, suggesting nuclear and nucleolar localization.

20 GO Annotation

9 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00000516
• Start: 7811240
• End: 7812105
• Strand: 1

20 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 866

1 Sequence Ontology Term

• Name: gene

2 Strains

• WBStrain00035555
• WBStrain00050664

1 Upstream Intergenic Region

• WormBase ID: intergenic_region_chrII_7809410..7811239
• Length (nt): 1830
• Chromosome Location: II: 7809410-7811239
• Organism: Caenorhabditis elegans