12.植物表观遗传
相关主题
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
Regulatory roles of chromatin if yes: EPIGENETIC REGULATION
if no: CHROMATIN REGULATION
Epigenetic/chromatin phenomena
Chromatin-based restriction of genome accessibility during differentiation Selective activation of genome after perception of stimulus (influence of environment/stress) Mitotic maintenance of cell identity (or loss thereof in cancer) Dosage compensation in the male versus female genome (X inactivation in mammals) Memory, Behavior, Aging
• Chromatin modifications are required for the proper expression of constitutively expressed or developmentally regulated genes
– Developmental abnormalities in many chromatin modification mutants – Developmentally regulated genes are associated with different modifications depending on whether they are “on” or “off”
Histone modification & transcription
H3K27me3 is required for tissue-specific gene repression
– Tissue-specific of H3K27me3 at a few known genes anti-correlated with expression level
Plant Epigenetics
Father of Genetics, discovered the basic laws of heredity.
Gregor Mendel (1822-1884)
Thomas Hunt Morgan
(1966-1945)
Discovered the 3rd basic genetic law, together with Mendel’s two laws, they form the basis of what is now known as classical genetics.
Thurman et al, Nat 2012
Histone post-translational modifications
Histone modifications in Arabidopsis
H2A H2B H3 H4
Histone lysines can be reversibly mono-, di- and trimethylated
Epigenetics vs Genetics
Components
A: Nucleosome
* Position
* Chromatin accessibility * Higher order chromatin interactions
B: Histone modifications C: DNA methylation D: Non-coding RNA (e.g. microRNA)
Mendelian Genetics
Change in nucleotide sequence
Alteration in gene expression and/or function
Novel phenotype
Monozygous twins share a common genotype and are genetically identicalwenku.baidu.com
Nucleosome
• Location of a nucleosome • Multiple isoforms of the histones • Covalent histone modifications
Where are the nucleosomes in plants?
Nucleosome occupancy and positioning are critical to biological outcomes, primarily because nucleosomes inhibit the access of other DNA-binding proteins to DNA.
Molecular Mechanisms – DNA methylation
• DNA sequence made up of 4 chemical bases; adenosine, guanine, tyrosine and cytosine (A,G,T,C) • One base, cytosine is epigenetically modified by DNA methylation
All heritable changes in gene expression and chromatin organization that are independent of the DNA sequence itself.
* These changes may remain through cell divisions for the remainder of the cell's life and may also last for multiple generations.
Epigenetic informations
Histone variant deposition
CH3 H2A H4 CH3CH » Nucleosome positioning DNA methylation
H3
N
H2B
N
Histone modification & recognition
Noncoding RNA
• Modification alter 3-D structure and make DNA more, or less, accessible
• Acetylation found in regions of increased gene expression
DNA-methylation and chromatin interact – differential recruitment of histones
Canonical histones and histone variants
Mechanism exist to “open up” chromatin
Chromatin remodeling, histone modifications
Mechanism exist to “condense” chromatin
Chromosomes consist of heterochromatin and euchromatin
Densely packaged heterochromatin
CENTROMERE DNA around the centromere is usually packaged as heterochromatin. Less densely packaged euchromatin
* ‘On’ or ‘over’ the genetic information encoded in the DNA • Development and differentiation • Maintenance of cellular identity * Epigenome provides instructions and regulates the functional aspects of all the genes
There is significant phenotypic discordance: Mental disorders Cancer
DNA Is Not Destiny
The cells are genetically identical, but different!
What is epigenetics?
Effects on replication, recombination, repair, and transcription
DNA methylation
In establishing heterochromatin, which is the driving force – DNA methylation? - Histone modification?
James Watson & Francis Crick
Elucidation of the “double helix structure” of DNA molecule is one of the most important scientific discovery in the 20th century, which symbols the birth of Molecular Genetics.
Histone modifications, DNA methylation, chromatin binding proteins
Can alter gene activity without change in DNA
Is it the existing chromatin state heritable?
Ling et al, MCB 2010
DHS Peaks Capture Most TF Binding Sites
• Motif occurrence in the DHS peaks suggest TF binding • Quantitative signal strength also suggest binding stability
• Encoded DNA information (i.e. ‘C’) remains the same • Epigenetic code has changed… • DNA methylation generally = suppression of gene activity
Zhang et al., 2007
H3K27me3 Activation
H3K23ac Promotor Repressed Gene H4k8ac H4k12ac H4K16ac
H3K36me1 H3K36me3 H3K36me2
H3K4me3 /H3K4me2 H3K4me1 Repression Promotor Active Gene
DNase Hypersensitive (HS) Mapping
• DNase randomly cuts genome (more often in open chromatin region) • Select short fragments (two nearby cuts) to sequence • Map to active promoters and enhancers
HKMT : histone lysine methyltransferase HDM : histone demethylases
Molecular Mechanisms – histone modifications
• Modifications of residues in the histone ‘tails’ • >40 possible modifications
if no: CHROMATIN REGULATION
Epigenetic/chromatin phenomena
Chromatin-based restriction of genome accessibility during differentiation Selective activation of genome after perception of stimulus (influence of environment/stress) Mitotic maintenance of cell identity (or loss thereof in cancer) Dosage compensation in the male versus female genome (X inactivation in mammals) Memory, Behavior, Aging
• Chromatin modifications are required for the proper expression of constitutively expressed or developmentally regulated genes
– Developmental abnormalities in many chromatin modification mutants – Developmentally regulated genes are associated with different modifications depending on whether they are “on” or “off”
Histone modification & transcription
H3K27me3 is required for tissue-specific gene repression
– Tissue-specific of H3K27me3 at a few known genes anti-correlated with expression level
Plant Epigenetics
Father of Genetics, discovered the basic laws of heredity.
Gregor Mendel (1822-1884)
Thomas Hunt Morgan
(1966-1945)
Discovered the 3rd basic genetic law, together with Mendel’s two laws, they form the basis of what is now known as classical genetics.
Thurman et al, Nat 2012
Histone post-translational modifications
Histone modifications in Arabidopsis
H2A H2B H3 H4
Histone lysines can be reversibly mono-, di- and trimethylated
Epigenetics vs Genetics
Components
A: Nucleosome
* Position
* Chromatin accessibility * Higher order chromatin interactions
B: Histone modifications C: DNA methylation D: Non-coding RNA (e.g. microRNA)
Mendelian Genetics
Change in nucleotide sequence
Alteration in gene expression and/or function
Novel phenotype
Monozygous twins share a common genotype and are genetically identicalwenku.baidu.com
Nucleosome
• Location of a nucleosome • Multiple isoforms of the histones • Covalent histone modifications
Where are the nucleosomes in plants?
Nucleosome occupancy and positioning are critical to biological outcomes, primarily because nucleosomes inhibit the access of other DNA-binding proteins to DNA.
Molecular Mechanisms – DNA methylation
• DNA sequence made up of 4 chemical bases; adenosine, guanine, tyrosine and cytosine (A,G,T,C) • One base, cytosine is epigenetically modified by DNA methylation
All heritable changes in gene expression and chromatin organization that are independent of the DNA sequence itself.
* These changes may remain through cell divisions for the remainder of the cell's life and may also last for multiple generations.
Epigenetic informations
Histone variant deposition
CH3 H2A H4 CH3CH » Nucleosome positioning DNA methylation
H3
N
H2B
N
Histone modification & recognition
Noncoding RNA
• Modification alter 3-D structure and make DNA more, or less, accessible
• Acetylation found in regions of increased gene expression
DNA-methylation and chromatin interact – differential recruitment of histones
Canonical histones and histone variants
Mechanism exist to “open up” chromatin
Chromatin remodeling, histone modifications
Mechanism exist to “condense” chromatin
Chromosomes consist of heterochromatin and euchromatin
Densely packaged heterochromatin
CENTROMERE DNA around the centromere is usually packaged as heterochromatin. Less densely packaged euchromatin
* ‘On’ or ‘over’ the genetic information encoded in the DNA • Development and differentiation • Maintenance of cellular identity * Epigenome provides instructions and regulates the functional aspects of all the genes
There is significant phenotypic discordance: Mental disorders Cancer
DNA Is Not Destiny
The cells are genetically identical, but different!
What is epigenetics?
Effects on replication, recombination, repair, and transcription
DNA methylation
In establishing heterochromatin, which is the driving force – DNA methylation? - Histone modification?
James Watson & Francis Crick
Elucidation of the “double helix structure” of DNA molecule is one of the most important scientific discovery in the 20th century, which symbols the birth of Molecular Genetics.
Histone modifications, DNA methylation, chromatin binding proteins
Can alter gene activity without change in DNA
Is it the existing chromatin state heritable?
Ling et al, MCB 2010
DHS Peaks Capture Most TF Binding Sites
• Motif occurrence in the DHS peaks suggest TF binding • Quantitative signal strength also suggest binding stability
• Encoded DNA information (i.e. ‘C’) remains the same • Epigenetic code has changed… • DNA methylation generally = suppression of gene activity
Zhang et al., 2007
H3K27me3 Activation
H3K23ac Promotor Repressed Gene H4k8ac H4k12ac H4K16ac
H3K36me1 H3K36me3 H3K36me2
H3K4me3 /H3K4me2 H3K4me1 Repression Promotor Active Gene
DNase Hypersensitive (HS) Mapping
• DNase randomly cuts genome (more often in open chromatin region) • Select short fragments (two nearby cuts) to sequence • Map to active promoters and enhancers
HKMT : histone lysine methyltransferase HDM : histone demethylases
Molecular Mechanisms – histone modifications
• Modifications of residues in the histone ‘tails’ • >40 possible modifications