KDM4C

Lysine-specific demethylase 4C is an enzyme that in humans is encoded by the KDM4C gene.[5][6][7]

KDM4C
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2XDP, 2XML, 4XDO, 4XDP, 5FJK, 5FJH
Identifiers
Aliases	KDM4C, GASC1, JHDM3C, JMJD2C, TDRD14C, bA146B14.1, lysine demethylase 4C
External IDs	OMIM: 605469 MGI: 1924054 HomoloGene: 41004 GeneCards: KDM4C
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9p24.1 Start 6,720,863 bp[1] End 7,175,648 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 C3 Start 74,242,497 bp[2] End 74,405,860 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • oxidoreductase activity • histone demethylase activity (H3-K9 specific) • dioxygenase activity • metal ion binding • chromatin binding • enzyme binding • histone demethylase activity • androgen receptor binding • zinc ion binding • histone demethylase activity (H3-K36 specific) • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific • methylated histone binding Cellular component • cell nucleus • nucleoplasm • nuclear chromatin • pericentric heterochromatin • histone methyltransferase complex Biological process • regulation of transcription from RNA polymerase II promoter • regulation of transcription, DNA-templated • oxidation-reduction process • transcription, DNA-templated • positive regulation of cell proliferation • blastocyst formation • regulation of gene expression • positive regulation of gene expression • histone H3-K9 demethylation • positive regulation of neuron differentiation • negative regulation of histone H3-K9 trimethylation • regulation of stem cell population maintenance • regulation of stem cell differentiation • histone H3-K36 demethylation • chromatin organization • negative regulation of transcription from RNA polymerase II promoter • chromatin remodeling • stem cell population maintenance Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	23081	76804
Ensembl	ENSG00000107077	ENSMUSG00000028397
UniProt	Q9H3R0	Q8VCD7
RefSeq (mRNA)	NM_001146694 NM_001146695 NM_001146696 NM_001304339 NM_001304340 NM_001304341 NM_015061 NM_001353997 NM_001353998 NM_001353999 NM_001354000 NM_001354001	NM_001172095 NM_144787 NM_001356561
RefSeq (protein)	NP_001140167 NP_001140168 NP_001291268 NP_001291269 NP_001291270 NP_055876 NP_001340926 NP_001340927 NP_001340928 NP_001340929 NP_001340930	NP_001165566 NP_659036 NP_001343490
Location (UCSC)	Chr 9: 6.72 – 7.18 Mb	Chr 4: 74.24 – 74.41 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene is a member of the Jumonji domain 2 (JMJD2) family and encodes a protein with one JmjC domain, one JmjN domain, two PHD-type zinc fingers, and two Tudor domains. This nuclear protein belongs to the alpha-ketoglutarate-dependent hydroxylase superfamily. It functions as a trimethylation-specific demethylase, converting specific trimethylated histone residues to the dimethylated form. Chromosomal aberrations and increased transcriptional expression of this gene are associated with esophageal squamous cell carcinoma.[7] A expressional decrease of KDM4C was found during cardiac differentation of murine embryonic stem cells.[8]

Model organisms

Kdm4c knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Abnormal[9]
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Abnormal
Eye Histopathology	Normal
Salmonella infection	Normal[10]
Citrobacter infection	Normal[11]
All tests and analysis from[12][13]

Model organisms have been used in the study of KDM4C function. A conditional knockout mouse line, called Kdm4c^{tm1a(KOMP)Wtsi}[14][15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.[12] Homozygous mutant males had decreased haematocrit and haemoglobin levels, while animals of both sex displayed an increase in sebaceous gland size.[12]

References

1. GRCh38: Ensembl release 89: ENSG00000107077 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028397 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Oct 1998). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (5): 277–86. doi:10.1093/dnares/5.5.277. PMID 9872452.
6. Katoh M, Katoh M (Jun 2004). "Identification and characterization of JMJD2 family genes in silico". International Journal of Oncology. 24 (6): 1623–8. doi:10.3892/ijo.25.3.759. PMID 15138608.
7. "Entrez Gene: JMJD2C jumonji domain containing 2C".
8. Boeckel, Jes-Niels; Derlet, Anja; Glaser, Simone F.; Luczak, Annika; Lucas, Tina; Heumüller, Andreas W.; Krüger, Marcus; Zehendner, Christoph M.; Kaluza, David (July 2016). "JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells". Arteriosclerosis, Thrombosis, and Vascular Biology. 36 (7): 1425–1433. doi:10.1161/ATVBAHA.116.307695. ISSN 1524-4636. PMID 27199445.
9. "Haematology data for Kdm4c". Wellcome Trust Sanger Institute.
10. "Salmonella infection data for Kdm4c". Wellcome Trust Sanger Institute.
11. "Citrobacter infection data for Kdm4c". Wellcome Trust Sanger Institute.
12. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
13. Mouse Resources Portal, Wellcome Trust Sanger Institute.
14. "International Knockout Mouse Consortium".
15. "Mouse Genome Informatics".
16. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
17. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
18. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
19. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Yang ZQ, Imoto I, Fukuda Y, Pimkhaokham A, Shimada Y, Imamura M, Sugano S, Nakamura Y, Inazawa J (Sep 2000). "Identification of a novel gene, GASC1, within an amplicon at 9p23-24 frequently detected in esophageal cancer cell lines". Cancer Research. 60 (17): 4735–9. PMID 10987278.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (Jan 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y (May 2006). "Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases". Cell. 125 (3): 467–81. doi:10.1016/j.cell.2006.03.028. PMID 16603238.
• Cloos PA, Christensen J, Agger K, Maiolica A, Rappsilber J, Antal T, Hansen KH, Helin K (Jul 2006). "The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3". Nature. 442 (7100): 307–11. doi:10.1038/nature04837. PMID 16732293.
• Wissmann M, Yin N, Müller JM, Greschik H, Fodor BD, Jenuwein T, Vogler C, Schneider R, Günther T, Buettner R, Metzger E, Schüle R (Mar 2007). "Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression". Nature Cell Biology. 9 (3): 347–53. doi:10.1038/ncb1546. PMID 17277772.
• Katoh Y, Katoh M (Aug 2007). "Comparative integromics on JMJD2A, JMJD2B and JMJD2C: preferential expression of JMJD2C in undifferentiated ES cells". International Journal of Molecular Medicine. 20 (2): 269–73. doi:10.3892/ijmm.20.2.269. PMID 17611647.
• Erhu Zhao, Jane Ding,.....Hongjuan Cui, Han-Fei Ding (2016). "KDM4C and ATF4 Cooperate in Transcriptional Control of Amino Acid Metabolism". Cell Reports. 14: 506–519. doi:10.1016/j.celrep.2015.12.053. PMC 4731315. PMID 26774480.CS1 maint: uses authors parameter (link)