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SUGAR-SENSING EPIGENOME BIOMARKER

Foreign code F170009029
File No. (S2015-2043-N0)
Posted date Mar 29, 2017
Country WIPO
International application number 2016JP076497
International publication number WO 2017043593
Date of international filing Sep 8, 2016
Date of international publication Mar 16, 2017
Priority data
  • P2015-177176 (Sep 9, 2015) JP
Title SUGAR-SENSING EPIGENOME BIOMARKER
Abstract An antibody of the present invention specifically bonds to a serine 40 residue modified with N-acetylglucosamine (GlcNAc) in a histone H2A protein. The present invention provides a method for detecting GlcNAc-modification of a serine 40 residue in a histone H2A protein, said method having a step for measuring the level of GlcNAc-modification of the serine 40 residue in the histone H2A protein using the antibody. A protein or a peptide marker of the present invention is a marker for monitoring histone modification caused by fluctuations in the concentration of extracellular glucose, said marker comprising an H2A protein, or a peptide fragment thereof, that contains a GlcNAc-modified serine 40 residue.
Outline of related art and contending technology BACKGROUND ART
Chromatin structure, in order to modulate the function of the genome, in the histone protein can be controlled by various modifications have been known. In such chemical modifications, post-translational modifications of histone protein is the critical determinant of chromatin remodeling as has been made clear, specific combinations of reversible histone modification is, the activated state of the chromatin is thought to affect. This specific combination is generated in the post-(epigenetically), despite the fact that the stable, and several of these may be cell activity in response to extracellular state temporarily reconfigured. The genome is a long-term control HDAC system and plays, a role for the genome of the cell control HDAC or modification, as a basis for the occurrence of cell differentiation is important, that can cause disease bankruptcy. The current, and the numerous known modifications include HDAC, wherein, at the end of the specific residues in histone acetylation of histone protein, methylation, ubiquitination is the control of gene expression associated with genome stability is known.
In recent years, as a modified histone protein as described above, to reduce N- acetylglucosamine (GlcNAc), new imprinted HDAC histone protein revealed that the phenomenon. GlcNAc-reversible phenomenon, N- acetylglucosamine transferase modification reaction can be coupled O- O - (OGT) and enzyme-bound N- acetylglucosamine (OGA) are catalyzed by two enzymes. N- Acetyl Glucosamine, the hexosamine biosynthetic pathway (HBP) generated in the cytosol by obtained from UDP-GlcNAc. The source of the first UDP-GlcNAc for extracellular glucose, degree of vitrification GlcNAc in the extracellular glucose concentration and cells are believed to vary with active HBP (for example, see non-patent document 1.). In addition, the long-term cell glucose and function of the changes in the genome, which may cause various diseases listed (for example, see non-patent document 2.).
GlcNAc of the activation of the amino acid in the histone protein, serine or threonine is known. Of the histone protein, and has now been found that GlcNAc-site is, from the end H2B of the amino acid sequence of the histone N 36 th serine, threonine of the 52 th, 55 th serine, serine of the 56 th, 64 th serine, serine of the 91 th, 112 th 123 th serine and serine, the amino acid sequence of histone H2A from the end of the 101 th threonine N, of the amino acid sequence of histone H3 or H3.3 from the end of the 10 th N serine, threonine and 80 th 32 th threonine, histone H4 from the end 47 of the amino acid sequence of the serine at position N in (for example, non-patent document 3, the reference 4.).
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • THE UNIVERSITY OF TOKYO
  • Inventor
  • SHIOTA Kunio
  • TAKAMORI Mitsuko
  • HAYAKAWA Koji
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG

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