GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:19727073

From GONUTS
Jump to: navigation, search
Citation

Ciccone, DN, Su, H, Hevi, S, Gay, F, Lei, H, Bajko, J, Xu, G, Li, E and Chen, T (2009) KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints. Nature 461:415-8

Abstract

Differential DNA methylation of the paternal and maternal alleles regulates the parental origin-specific expression of imprinted genes in mammals. The methylation imprints are established in male and female germ cells during gametogenesis, and the de novo DNA methyltransferase DNMT3A and its cofactor DNMT3L are required in this process. However, the mechanisms underlying locus- and parental-specific targeting of the de novo DNA methylation machinery in germline imprinting are poorly understood. Here we show that amine oxidase (flavin-containing) domain 1 (AOF1), a protein related to the lysine demethylase KDM1 (also known as LSD1), functions as a histone H3 lysine 4 (H3K4) demethylase and is required for de novo DNA methylation of some imprinted genes in oocytes. AOF1, now renamed lysine demethylase 1B (KDM1B) following a new nomenclature, is highly expressed in growing oocytes where genomic imprints are established. Targeted disruption of the gene encoding KDM1B had no effect on mouse development and oogenesis. However, oocytes from KDM1B-deficient females showed a substantial increase in H3K4 methylation and failed to set up the DNA methylation marks at four out of seven imprinted genes examined. Embryos derived from these oocytes showed biallelic expression or biallelic suppression of the affected genes and died before mid-gestation. Our results suggest that demethylation of H3K4 is critical for establishing the DNA methylation imprints during oogenesis.

Links

PubMed Online version:10.1038/nature08315

Keywords

Alleles; Animals; DNA Methylation; Embryo Loss/genetics; Embryo, Mammalian/metabolism; Female; Gene Expression Regulation, Developmental; Genes, Developmental/genetics; Genomic Imprinting; Histones/metabolism; Male; Mice; Mothers; NIH 3T3 Cells; Oocytes/metabolism; Oxidoreductases, N-Demethylating/deficiency; Oxidoreductases, N-Demethylating/genetics; Oxidoreductases, N-Demethylating/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:KDM1B

enables

GO:0140682: histone H3-di/monomethyl-lysine-4 FAD-dependent demethylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:KDM1B

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:KDM1B

acts_upstream_of_or_within

GO:0006349: regulation of gene expression by genetic imprinting

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4359289

P

Seeded From UniProt

complete

MOUSE:KDM1B

acts_upstream_of_or_within

GO:0043046: DNA methylation involved in gamete generation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:4359289

P

  • occurs_in:(CL:0000023)

Seeded From UniProt

complete

MOUSE:KDM1B

acts_upstream_of_or_within

GO:0034720: histone H3-K4 demethylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM1B

NOT|enables

GO:0034647: histone H3-tri/di/monomethyl-lysine-4 demethylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:KDM1B

involved_in

GO:0006349: regulation of gene expression by genetic imprinting

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM1B

involved_in

GO:0044030: regulation of DNA methylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:KDM1B

involved_in

GO:0034720: histone H3-K4 demethylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:KDM1B

located_in

GO:0005634: nucleus

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8CIG3

C

Seeded From UniProt

complete

HUMAN:KDM1B

involved_in

GO:0006349: regulation of gene expression by genetic imprinting

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8CIG3

P

Seeded From UniProt

complete

HUMAN:KDM1B

involved_in

GO:0044030: regulation of DNA methylation

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8CIG3

P

Seeded From UniProt

complete

HUMAN:KDM1B

involved_in

GO:0034720: histone H3-K4 demethylation

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8CIG3

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.