生物信息学 第11章 转录调控的信息学分析
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第十一章 转录调控的信息学分析
Bioinformatic Analysis of Transcriptional Regulation
第一节 引 言
Introduction
基因转录调节的基本模式
transcription factor
cis-regulatory element
• In an equilibrium model, the state of a binding site on DNA depends on the concentration of the protein that binds to it.
• Suppose that the DNA sequence is organized into nucleosomes in only one particular configuration, so that each site on the DNA always is located at a particular position on the nucleosome. This type of organization is called nucleosome positioning (or sometimes nucleosome phasing).
• Whether a gene is expressed depends on the structure of chromatin both locally (at the promoter) and in the surrounding domain.
• Chromatin structure correspondingly can be regulated by individual activation events or by changes that affect a wide chromosomal region.
simultaneous depending on the gene.
MethyLation of Histones and DNA
Is Connected
• Acetylation of histones activates chromatin, and methylation of DNA and histones inactivates chromatin.
• Promoter activation involves binding of a sequence-specific activator, recruitment and action of a remodeling complex, and recruitment and action of an acetylating complex. The order of events can differ or can even be
Some Common Motifs Are Found in Proteins That Modify Chromatin
• The chromodomain is found in several chromatin proteins that have either activating or repressing effects on gene expression.
• The most localized events concern an individual target gene, where changes in nucleosomal structure and organization occur in the immediate vicinity of the promoter.
Epigenetic Effects Are Inherited
• Replication of a methylated site produces hemimethylated DNA, in which only the parental strand is methylated. A perpetuation methylase recognizes hemimethylated sites and adds a methyl group to the base on the daughter strand. This restores the original situation, in which the site is methylated on both strands. A nonmethylated site remains non methylated after replication.
• Nucleosome positioning places restriction sites at unique positions relative to the linker sites cleaved by micrococcal nuclease.
Chromatin Can Have Alternative States
• The SET domain is part of the catalytic site of protein methyltransferases.
• The bromodomain is found in a variety of proteins that interact with chromatin and is used to recognize acetylated sites on histones.
Chromatin Remodeling Is an Active Process
• The dynamic model for transcription of chromatin relies upon factors that can use energy provided by hydrolysis of ATP to displace nucleosomes from specific DNA sequences.
• The MMTV promoter requires a change in rotational positioning of a nucleosome to allow an activator to bind to DNA on the nucleosome.
Histone Modification Is a Key Event
A.The state of methylated sites could be perpetuated by an enzyme that recognizes only hemimethylated sites as substrates.
• How are acetylases (or deacetylases) recruited to their specific targets? As we have seen with remodeling complexes, the process is likely to be indirect.
• This is not, however, a simple rule, and the particular sites that are modified (as well as combinations of specific modifications) may be important
maintenance methylase.
A
B
B. The state of methylation is controlled by three types of enzyme. De novo and perpetuation methylases are known, but demethylases have not been identified.
• We now know that this occurs largely because of acetylation of the nucleosomes in the vicinity of the promoter when a gene is activated.
Promoter Activation Involves an Ordered Series of Events
Nucleosome Organization May Be Changed atwk.baidu.comthe Promoter
• Remodeling complexes are recruited to promoters by sequence-specific activators.
• The factor may be released once the remodeling complex has bound.
• Acetylation associated with gene activation occurs by directly modifying histones in nucleosomes.
• Acetylation of histones in chromatin is generally correlated with the state of gene expression.
• The Nucleosome Is the Subunit of All Chromatin
• The nucleosome may be a cylinder with DNA organized into two turns around the surface.
• Sequences on the DNA that lie on different turns around the nucleosome may be close together.
• Remodeling complexes can cause nucleosomes to slide along DNA, can displace nucleosomes from DNA, or can reorganize the spacing between nucleosomes.
DNA Methylation Is Perpetuated by a Maintenance Methylase
1. Most methyl groups in DNA are found on cytosine on both strands of the CpG doublet.
2. Replication converts a fully methylated site to a hemimethylated site. 3. Hemimethylated sites are converted to fully methylated sites by a
• Histones are modified by methyLation, acetyLation, and phosphoryLation.
• Acetylation of H3 and H4 is associated with active chromatin, whereas methylation is associated with inactive chromatin.
Histone Acetylation Occurs in Two
Circumstances
• Acetylation at replication occurs on histones before they are incorporated into nucleosomes.
• When chromosomes are replicated, which occurs during the S phase of the cell cycle, histones are transiently acetylated.
Bioinformatic Analysis of Transcriptional Regulation
第一节 引 言
Introduction
基因转录调节的基本模式
transcription factor
cis-regulatory element
• In an equilibrium model, the state of a binding site on DNA depends on the concentration of the protein that binds to it.
• Suppose that the DNA sequence is organized into nucleosomes in only one particular configuration, so that each site on the DNA always is located at a particular position on the nucleosome. This type of organization is called nucleosome positioning (or sometimes nucleosome phasing).
• Whether a gene is expressed depends on the structure of chromatin both locally (at the promoter) and in the surrounding domain.
• Chromatin structure correspondingly can be regulated by individual activation events or by changes that affect a wide chromosomal region.
simultaneous depending on the gene.
MethyLation of Histones and DNA
Is Connected
• Acetylation of histones activates chromatin, and methylation of DNA and histones inactivates chromatin.
• Promoter activation involves binding of a sequence-specific activator, recruitment and action of a remodeling complex, and recruitment and action of an acetylating complex. The order of events can differ or can even be
Some Common Motifs Are Found in Proteins That Modify Chromatin
• The chromodomain is found in several chromatin proteins that have either activating or repressing effects on gene expression.
• The most localized events concern an individual target gene, where changes in nucleosomal structure and organization occur in the immediate vicinity of the promoter.
Epigenetic Effects Are Inherited
• Replication of a methylated site produces hemimethylated DNA, in which only the parental strand is methylated. A perpetuation methylase recognizes hemimethylated sites and adds a methyl group to the base on the daughter strand. This restores the original situation, in which the site is methylated on both strands. A nonmethylated site remains non methylated after replication.
• Nucleosome positioning places restriction sites at unique positions relative to the linker sites cleaved by micrococcal nuclease.
Chromatin Can Have Alternative States
• The SET domain is part of the catalytic site of protein methyltransferases.
• The bromodomain is found in a variety of proteins that interact with chromatin and is used to recognize acetylated sites on histones.
Chromatin Remodeling Is an Active Process
• The dynamic model for transcription of chromatin relies upon factors that can use energy provided by hydrolysis of ATP to displace nucleosomes from specific DNA sequences.
• The MMTV promoter requires a change in rotational positioning of a nucleosome to allow an activator to bind to DNA on the nucleosome.
Histone Modification Is a Key Event
A.The state of methylated sites could be perpetuated by an enzyme that recognizes only hemimethylated sites as substrates.
• How are acetylases (or deacetylases) recruited to their specific targets? As we have seen with remodeling complexes, the process is likely to be indirect.
• This is not, however, a simple rule, and the particular sites that are modified (as well as combinations of specific modifications) may be important
maintenance methylase.
A
B
B. The state of methylation is controlled by three types of enzyme. De novo and perpetuation methylases are known, but demethylases have not been identified.
• We now know that this occurs largely because of acetylation of the nucleosomes in the vicinity of the promoter when a gene is activated.
Promoter Activation Involves an Ordered Series of Events
Nucleosome Organization May Be Changed atwk.baidu.comthe Promoter
• Remodeling complexes are recruited to promoters by sequence-specific activators.
• The factor may be released once the remodeling complex has bound.
• Acetylation associated with gene activation occurs by directly modifying histones in nucleosomes.
• Acetylation of histones in chromatin is generally correlated with the state of gene expression.
• The Nucleosome Is the Subunit of All Chromatin
• The nucleosome may be a cylinder with DNA organized into two turns around the surface.
• Sequences on the DNA that lie on different turns around the nucleosome may be close together.
• Remodeling complexes can cause nucleosomes to slide along DNA, can displace nucleosomes from DNA, or can reorganize the spacing between nucleosomes.
DNA Methylation Is Perpetuated by a Maintenance Methylase
1. Most methyl groups in DNA are found on cytosine on both strands of the CpG doublet.
2. Replication converts a fully methylated site to a hemimethylated site. 3. Hemimethylated sites are converted to fully methylated sites by a
• Histones are modified by methyLation, acetyLation, and phosphoryLation.
• Acetylation of H3 and H4 is associated with active chromatin, whereas methylation is associated with inactive chromatin.
Histone Acetylation Occurs in Two
Circumstances
• Acetylation at replication occurs on histones before they are incorporated into nucleosomes.
• When chromosomes are replicated, which occurs during the S phase of the cell cycle, histones are transiently acetylated.