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Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human histone deacetylases I (HDAC1) and II (HDAC2) are homologous proteins (84% identity) that catalyze release of acetyl groups from modified N-terminal lysines of core histones. Histone deacetylation is correlated with both transient and persistent states of transcriptional inactivity (i.e. silencing) in many eukaryotes. In this study, we analyzed complexes containing HDAC1 and HDAC2 to identify the proteins most stably associated with these deacetylases. Complex cI (9.5 S) contained transcriptional corepressor CoREST/kiaa0071 and a protein homologous to FAD-dependent oxidoreductases, kiaa0601. Complex cII (15 S) contained >/=15 proteins, including CHD3/4 (Mi-2), Mta-L1, RbAp48/46, and MBD3, characteristic of vertebrate nucleosome-remodeling complexes. Under native conditions, cI and cII may contain HDAC1, HDAC2 or both; these can be dissociated to cI and cII core complexes containing only HDAC1 or HDAC2. The (m)CpG-binding protein MBD2 was associated only with the HDAC1 cII core complex. A model is proposed in which HDAC1 core complexes can be targeted to methylated DNA via MBD2 with recruitment of HDAC2 occurring through formation of HDAC1/2 cII dimers. We note that the cI component CoREST/kiaa0071 and the cII component Mta-L1 share a region of homology that includes a SANT domain; this domain may play a role in complex assembly.
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PMID:Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1. 1110 43

Histone lysine and arginine residues are subject to a wide array of post-translational modifications including methylation, citrullination, acetylation, ubiquitination, and sumoylation. The combinatorial action of these modifications regulates critical DNA processes including replication, repair, and transcription. In addition, enzymes that modify histone lysine and arginine residues have been correlated with a variety of human diseases including arthritis, cancer, heart disease, diabetes, and neurodegenerative disorders. Thus, it is important to fully understand the detailed kinetic and chemical mechanisms of these enzymes. Here, we review recent progress towards determining the mechanisms of histone lysine and arginine modifying enzymes. In particular, the mechanisms of S-adenosyl-methionine (AdoMet) dependent methyltransferases, FAD-dependent demethylases, iron dependent demethylases, acetyl-CoA dependent acetyltransferases, zinc dependent deacetylases, NAD(+) dependent deacetylases, and protein arginine deiminases are covered. Particular attention is paid to the conserved active-site residues necessary for catalysis and the individual chemical steps along the catalytic pathway. When appropriate, areas requiring further work are discussed.
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PMID:Chemical mechanisms of histone lysine and arginine modifications. 1860 28

Histone methylation and demethylation are important processes associated with the regulation of gene transcription, and alterations in histone methylation status have been linked to a large number of human diseases. Initially thought to be an irreversible process, histone methylation is now known to be reversed by two families of proteins containing over 30 members that act to remove methyl groups from specific lysine residues present in the tails of histone H3 and histone H4. A rapidly growing number of reports have implicated the FAD-dependent lysine specific demethylase (KDM1) family in cancer, and several small-molecule inhibitors are in development for the treatment of cancer. An additional role has emerged for KDM1 in brain function, offering additional opportunities for the development of novel therapeutic strategies in neurodegenerative disease. A decade after the identification of KDM1A as a histone demethylase, the first selective inhibitors have now reached the clinic.
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PMID:KDM1 histone lysine demethylases as targets for treatments of oncological and neurodegenerative disease. 2611 Oct 32

Histone lysine methylation is one of the posttranslational modifications involved in transcriptional regulation and chromatin remodeling. The first lysine specific histone demethylase (LSD1) has been recently discovered, whichrules out the hypothesis that histone methylation represents a permanent epigenetic mark. LSD1 (previously known as KIAA0601) has been typically found in association with CoREST (a corepressor protein) and histone deacetylases 1 and 2, forming a highly conserved core complex. These proteins have been shown to be part of several megadalton corepressor complexes, which are proposed to operate in the context of a stable and extended form of repression through silencing of entire chromatin domains. LSD1 is a FAD-dependent protein that specifically catalyzes the demethylation of Lys4 of histone H3 by an oxidative process. The amino acid sequence of the human enzyme (90 kDa) has a modular organization with an N-terminal SWIRM domain, which has been found to mediate protein-protein interactions, and a C-terminal domain similar to FAD-dependent amine oxidases. Three assays based on different events of the demethylation reaction can be used to study LSD1 biochemical properties. The strict substrate specificity of LSD1 suggests the existence of other putative histone lysine demethylases that may use alternative mechanisms for the regulation of this posttranslational modification.
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PMID:8 Demethylation pathways for histone methyllysine residues. 2671 42