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AOF1 is a histone H3K4 demethylase possessing demethylase activity-independent repression function. 2010

Ze Yang, and Jun Jiang, and M David Stewart, and David M Stewart, and Shankang Qi, and Kenichi Yamane, and Jiwen Li, and Yi Zhang, and Jiemin Wong
The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

LSD1 (KDM1 under the new nomenclature) was the first identified lysine-specific histone demethylase belonging to the flavin-dependent amine oxidase family. Here, we report that AOF1 (KDM1B under the new nomenclature), a mammalian protein related to LSD1, also possesses histone demethylase activity with specificity for H3K4me1 and H3K4me2. Like LSD1, the highly conserved SWIRM domain is required for its enzymatic activity. However, AOF1 differs from LSD1 in several aspects. First, AOF1 does not appear to form stable protein complexes containing histone deacetylases. Second, AOF1 is found to localize to chromosomes during the mitotic phase of the cell cycle, whereas LSD1 does not. Third, AOF1 represses transcription when tethered to DNA and this repression activity is independent of its demethylase activity. Structural and functional analyses identified its unique N-terminal Zf-CW domain as essential for the demethylase activity-independent repression function. Collectively, our study identifies AOF1 as the second histone demethylase in the family of flavin-dependent amine oxidases and reveals a demethylase-independent repression function of AOF1.

UI MeSH Term Description Entries
D008938 Mitosis A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species. M Phase, Mitotic,Mitotic M Phase,M Phases, Mitotic,Mitoses,Mitotic M Phases,Phase, Mitotic M,Phases, Mitotic M
D009865 Oocytes Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM). Ovocytes,Oocyte,Ovocyte
D010089 Oxidoreductases, N-Demethylating N-Demethylase,N-Demethylases,Oxidoreductases, N Demethylating,Demethylating Oxidoreductases, N,N Demethylase,N Demethylases,N Demethylating Oxidoreductases,N-Demethylating Oxidoreductases
D012097 Repressor Proteins Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release. Repressor Molecules,Transcriptional Silencing Factors,Proteins, Repressor,Silencing Factors, Transcriptional
D002875 Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Chromosome
D006655 Histone Deacetylases Deacetylases that remove N-acetyl groups from amino side chains of the amino acids of HISTONES. The enzyme family can be divided into at least three structurally-defined subclasses. Class I and class II deacetylases utilize a zinc-dependent mechanism. The sirtuin histone deacetylases belong to class III and are NAD-dependent enzymes. Class I Histone Deacetylases,Class II Histone Deacetylases,HDAC Proteins,Histone Deacetylase,Histone Deacetylase Complexes,Complexes, Histone Deacetylase,Deacetylase Complexes, Histone,Deacetylase, Histone,Deacetylases, Histone
D006657 Histones Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. Histone,Histone H1,Histone H1(s),Histone H2a,Histone H2b,Histone H3,Histone H3.3,Histone H4,Histone H5,Histone H7
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014158 Transcription, Genetic The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION. Genetic Transcription
D014981 Xenopus An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.

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