组蛋白糖基化修饰—杨彦龙

The O-GlcNAcylation of histones
The O-GlcNAcylation of histones
1. we demonstrate by multiple specific immunological and enzymatic approaches that histones are OGlcNAcylated in vivo.
Historical Background of O- GlcNAc
O-GlcNAc was first shown to be a major form of intracellular glycosylation in murine lymphocytes in 1984
O-Linked β-N-acetylglucosamine (O-GlcNAc) is a dynamic protein modification abundant within
Diverse Functions of O-GlcNAc Modification
transcription
signaling
protein–protein interactions
(2002) 6:851
Results
• 1.H1 histone ,as well as core histones ,may be mannosylated and N-acetylglucosaminylated
Glycosylation of H1 Histone in Murine Liver Nucleus korean biochem J(1994) vol.27,No.3 pp 240-244. • 3.Sakabe, K., Wang, Z., and Hart, G.W. (2010). β-N-acetylglucosamine (O-GlcNAc) is part of the histone code Proc.Natl. Acad. Sci. USA 107, 19915–19920. • 4. Hanover JA.（2010）. Epigenetics gets sweeter: O-GlcNAc joins the "histone code".Chem Biol. Dec 22;17(12):1272-4. • 5. Butkinaree, C., Park, K., and Hart, G.W. (2010).Biochim. Biophys. Acta 1800, 96– 106. • 6. Dona C. Lovea, Michael W. Krauseb, John A. Hanovera O-GlcNAc cycling: Emerging roles in development and epigenetics Seminars in Cell & Developmental Biology 21 (2010) 646–654 • 7. Love, D.C., Ghosh, S., Mondoux, M.A., Fukushige,T., Wang, P., Wilson, M.A., Iser, W.B., Wolkow, C.A., Krause, M.W., and Hanover, J.A. (2010a).Proc. Natl. Acad. Sci. USA 107, 7413–7418.
Histone H3 also bears O-GlcNAc.
there are Ser or Thr residues that are O-GlcNAcylated only in vivo.
2. O-GlcNAc link to epigenetics
• Direct link of OGlcNAcylation to PcGmediated gene silencing
• 4.O-GlcNAc cycling occurs on chromatin, particularly in promoter regions of genes involved in metabolism , stress, and aging
Discussion
• 1. More sites remain to be identified
O-GlcNAc is part of the histone code
Kun Ming institute of botany, CAS Yang Yan Long
Content
• 1. Historical Background of O- GlcNAc • 2. The O-GlcNAcylation of histones • 3. Role of histone O-GlcNAyclation • 4. Discussion
Role of histone O-GlcNAyclation
role in chromatin structure
• 2.O-GlcNAc directly affects chromatin remodelers
• 3. Direct link of O-GlcNAcylation to PcG-mediated gene silencing
组蛋白糖基化修饰—杨彦龙 histonecode kun ming institute botany,cas yang yan long content historicalbackground histoneo-glcnayclation discussionhistorical background glcnaco-glcnac firstshown majorform intracellularglycosylation murinelymphocytes 1984o-linkedβ-n-acetylglucosamine (o-glcnac) dynamicprotein modification abundant within cytoplasmchapter 18, figure glycobiologysecond edition chapter 18, figure glycobiologysecond edition o-glcnacylated proteins occur manydifferent cellular compartments o-glcnacylation exhibits complexdynamic interplay o-phosphorylationmultiple states o-glcnacmodification o-glcnac transferase (ogt) multiplecomplex mechanisms chapter 18, figure glycobiologysecond edition udp-glcnac o-glcnactransferase (ogt) idealsensor metabolicstatus celltranscription signaling protein–protein interactions diverse functions o-glcnacmodification (2002) 6:851 results 1.h1histone corehistones ,may h1histone corehistones may mammaliancells. 1.furtherstudies should focus radioactivemonosaccharides cellcycle related
• H2A: Thr101 • H2B： Ser36 • H 4： Ser47
Changes in histone O-GlcNAcylation in vivo
• 1. O-GlcNAc levels on histones decreased during mitosis and subsequently returned to basal levels in G1
• 2. Glycosylation of H1 histone and core histones may be conserved in mammalian cells.
• 1.Further studies should focus on the incorporation of radioactive monosaccharides into histone
the nucleus and cytoplasm
a
b
Essentials of Glycobiology Second Edition
Chapter 18, Figure 1
O-GlcNAcylated proteins occur in many different cellular compartments
a
b
Essentials of Glycobiology Second Edition
Chapter 18, Figure 2
O-GlcNAcylation exhibits a complex dynamic interplay with O-phosphorylation
Multiple States of O-GlcNAc Modification
• 2. In nucleo OGT assays also demonstrate that OGT activity toward histones decreases during mitosis
Changes in histone O-GlcNAcylation in vivo
1. O-GlcNAc levels on histones increased during the recovery after heat shock
2. Histones also are substrates for OGT in vitro
3. We identify O-GlcNAc sites on histones H2A, H2B, and H4 using mass spectrometry
map O-GlcNAc sites on histones
An O-GlcNAc link to Xinactivation
O-GlcNAc link to epigenetics
REFERENCES
• 1. Essentials of Glycobiology, 2nd edition • 2. Tae Hyoung Kim , Jin Yong Park , Sang Ho Lee , Hyo Ihl Chang(1994) Possible
• 2. Cell cycle related alteration of glycosylation in nuclear proteins to address the functions of glycosylation in the nuclear proteins
• 3. Direct analysis of carbohydrates in histones to confirm that they are glycosylated
O-GlcNAc transferase (OGT) is regulated by multiple complex mechanisms
Essentials of Glycobiology Second Edition
Chapter 18, Figure 6
UDP-GlcNAc is the donor for O-GlcNAc transferase (OGT) and an ideal sensor of the metabolic status of the cell
2. After recovery for 1 h, MNase digestion revealed that the chromatin had condensed even further, correlating with increased histone O-GlcNAcylation.