1 Histone Modifications and Histone Modifications and Cancer Cancer - Yu Zhang, Ph.D., ( - Yu Zhang, Ph.D., ( 张张 张张 ) ) - Institute of Genetics and - Institute of Genetics and Cytology, Cytology, School of Life Sciences, School of Life Sciences, - Northeast Normal University - Northeast Normal University
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1 Histone Modifications and Cancer - Yu Zhang, Ph.D., ( 张瑜 ) - Institute of Genetics and Cytology, School of Life Sciences, School of Life Sciences, -
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Histone Modifications and CancerHistone Modifications and Cancer
Histone Modifications and CancerHistone Modifications and Cancer
- Yu Zhang, Ph.D., (- Yu Zhang, Ph.D., ( 张瑜张瑜 ))- Institute of Genetics and Cytology,- Institute of Genetics and Cytology, School of Life Sciences,School of Life Sciences,- Northeast Normal University- Northeast Normal University
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• Histone code hypothesis
• Histone acetylation and deacetylation
• Histone lysine methylation
• Argine methylation and transcriptional regulation
• Histone modification in cancer
• Epigenetic diagnosis and therapies of cancer
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Definition of EpigeneticsDefinition of Epigenetics
Heritable and/or acquired changes in gene expression that occur without changes in DNA sequence.
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Histone code hypothesis
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Package of 2-meter long genomic DNA into nucleus of only Package of 2-meter long genomic DNA into nucleus of only a few micrometers. Nucleosomes as basic units.a few micrometers. Nucleosomes as basic units.
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Crystal diffraction of histone structure
8Chromatin organization and the tail of histone H3.
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The N-termini of core histones are active domains The N-termini of core histones are active domains
critical to DNA-protein interaction. Many specific amino critical to DNA-protein interaction. Many specific amino
acid residues in N-termini are subject to various covalent acid residues in N-termini are subject to various covalent
chemical modifications, such as chemical modifications, such as acetylationacetylation, , methylationmethylation, ,
Various modifications at defined sites of the core histone N-termini Various modifications at defined sites of the core histone N-termini constitute the “constitute the “histone codehistone code”.”.
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Histone acetylation and deacetylation
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CHEST 129 1 JAUNARY 2006
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TypeA HATs type B HATs
localized in nucleiacetylate nucleosomal histones
cytoplasmic fractionsacetylating newly synthesized histones before chromatin assembly during DNA replication.
Gcn5p and homologs PCAF, p300/CBP, TAFII250 and homologs, and SRC-1 and ACTR
• Acetylation/deacetylation of defined lysine residues of H3, Acetylation/deacetylation of defined lysine residues of H3, H4, H2A and H2B histones;H4, H2A and H2B histones;
• Catalyzed by histone acetyltransferase/deacetylase Catalyzed by histone acetyltransferase/deacetylase complexes (HAT/HDAC);complexes (HAT/HDAC);
• Hyperacetylation (high) Hyperacetylation (high) →→ open nucleosome and chromatin open nucleosome and chromatin structure → transcription activation;structure → transcription activation;
• A balanced acetylation level of the genome is critical to the A balanced acetylation level of the genome is critical to the normal function of the cell and organism.normal function of the cell and organism.