Core histones Ac AC Ac Ac Ac AC Ac C AC Ac Ac A AC Transcription ethylate Ac (MBD Methyl-CpG-binding protein HDAC Histone deacetylase MBD MBD MBD MBD) MBD TD MBD Model for methy lation-de pendent gene silencing. The structural element of chromatin is the nucleosomal core, which consists of a 146-bp DNA sequence wra pped around core histones. Acetylation of the histones causes an open chromatin config-uration that is associated with tra nscriptional activity. Methylated cytosines are recognized by methyl-CpG-binding proteins(MBDs), whic h in turn recruit histone deacetylases(DAcs)to the site of methylation, convert-ing the chromatin into a closed structure that can no longer be accessed by the transcriptio nal machinery
Model for methylation-dependent gene silencing. The structural element of chromatin is the nucleosomal core, which consists of a 146-bp DNA sequence wrapped around core histones. Acetylation of the histones causes an open chromatin config-uration that is associated with transcriptional activity. Methylated cytosines are recognized by methyl-CpG-binding proteins (MBDs), which in turn recruit histone deacetylases (HDACs) to the site of methylation, convert-ing the chromatin into a closed structure that can no longer be accessed by the transcriptional machinery
Inhibitors of histone deacetylase (e.g. trichostatin A) DNMT DNMr、HDA DNMT DNMT DNMT DNMT A DNMT DA Ac nhibitors of DNa methylation (e.g. 5-aza-2-deoxycytidine) Fig. The transcriptionally repressive state of chromatin mediated by promoter methylation may be alleviated by the action of inhibitors of DNA methylation or histone deacetylase. Cytosine analogues like 5aza 2 deoxycytidine are incorporated into the DNa and act as covalent inhibitors of DNA methyltransferase(DNMT). Inhibition of histone deacetylase(HDAC) favors the acetylation of core histones
组成核小体的组蛋白可以被多种化学加合物所 修饰,如磷酸化、乙酰化和甲基化等,组蛋白的这 类结构修饰可使染色质的构型发生改变,称为染色 质构型重塑。组蛋白中不同氨基酸残基的乙酰化一 般与活化的染色质构型常染色质( euchromatin和 有表达活性的基因相关联;而组蛋白的甲基化则与 浓缩的异染色质( hetero- chromatin和表达受抑 的基因相关联。 染色质重塑
组成核小体的组蛋白可以被多种化学加合物所 修饰，如磷酸化、乙酰化和甲基化等，组蛋白的这 类结构修饰可使染色质的构型发生改变，称为染色 质构型重塑。组蛋白中不同氨基酸残基的乙酰化一 般与活化的染色质构型常染色质(euchromatin)和 有表达活性的基因相关联；而组蛋白的甲基化则与 浓缩的异染色质(hetero-chromatin)和表达受抑 的基因相关联。 染色质重塑
Biological phenomena Transcription, Replication, Repair, Recombination Development, Reprogramming, Aging, Tumorigenesis DNA methylation Protein modification Epigenetics Chromatin Epigenetics is an advanced biological system that selectively utilizes genomic information and is involved in various fundamental phenomena. Specifically, it puts emphasis on the regulation of gene expression, through DNA methylation, chromatin, and post-translational modification of proteins such as histones. Arrows indicate possible functional interactions between them. DNA hypermethylation, histone hypoacetyl ation and inactive chromatin repress transcription. In contrast, a transcriptionally active condition may encourage dna hypomethylation, histone hyperacetylation and active chromatin. Also, a particular chromatin structure may e required for establishing DNA methylation
Epigenetics is an advanced biological system that selectively utilizes genomic information and is involved in various fundamental phenomena. Specifically, it puts emphasis on the regulation of gene expression, through DNA methylation, chromatin, and post-translational modification of proteins such as histones. Arrows indicate possible functional interactions between them. DNA hypermethylation, histone hypoacetylation and inactive chromatin repress transcription. In contrast, a transcriptionally active condition may encourage DNA hypomethylation, histone hyperacetylation and active chromatin. Also, a particular chromatin structure may be required for establishing DNA methylation
研究还表明,组蛋白甲基化可以与基因抑 制有关,也可以与基因的激活相关,这往往 取决于被修饰的赖氨酸处于什么位置。 例如,上述的H3Lys9甲基化最终导致了 基因的沉默;然而,位于H31s4的甲基化则与 基因的活化相关联
研究还表明，组蛋白甲基化可以与基因抑 制有关，也可以与基因的激活相关，这往往 取决于被修饰的赖氨酸处于什么位置。 例如，上述的H3 Lys9甲基化最终导致了 基因的沉默；然而，位于H3 Lys4的甲基化则与 基因的活化相关联