KDM4C

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 74,160,734 bp [2] End 74,324,097 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in bone marrow cells thymus Achilles tendon sural nerve corpus callosum body of pancreas monocyte rectum cerebellar vermis stomach Top expressed in saccule otic placode lacrimal gland retinal pigment epithelium interventricular septum pineal gland superior cervical ganglion olfactory epithelium iris salivary gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function oxidoreductase activity histone H3-methyl-lysine-9 demethylase activity dioxygenase activity metal ion binding chromatin binding enzyme binding histone demethylase activity androgen receptor binding zinc ion binding histone H3-methyl-lysine-36 demethylase activity DNA-binding transcription repressor activity, RNA polymerase II-specific methylated histone binding Cellular component nucleus nucleoplasm pericentric heterochromatin histone methyltransferase complex Biological process regulation of transcription by RNA polymerase II regulation of transcription, DNA-templated transcription, DNA-templated positive regulation of cell population 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 by RNA polymerase II 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: 74.16 – 74.32 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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. S2CID   85911512.
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. S2CID   18872015.
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. S2CID   14461740.
• 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. Bibcode:2006Natur.442..307C. doi:10.1038/nature04837. PMID   16732293. S2CID   2874903.
• 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. S2CID   26006234.
• 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.
• Zhao E, Ding J, Xia Y, Liu M, Ye B, Choi JH, Yan C, Dong Z, Huang S, Zha Y, Yang L, Cui H, Ding HF (2016). "KDM4C and ATF4 Cooperate in Transcriptional Control of Amino Acid Metabolism". Cell Reports. 14 (3): 506–519. doi:10.1016/j.celrep.2015.12.053. PMC   4731315 . PMID   26774480.