講義教程說明1

1、Part 3How Genomes Are ExpressedTranscription, translation and their regulationChapter 10:Accessing the GenomeChromosome package status, the accessibility10.1 Inside the nucleusThe DNA in the nucleus of a eukaryotic cell or the nucleoid of a prokaryote is attached to a variety of proteins that are no

2、t directly involved in genome expression and must be displaced in order for RNA polymerase and other expression proteins to gain access to the genes.Histones and other packaging proteins are not simply inert structures around which the DNA is woundThe nucleus has an ordered internal structureThe ins

3、ide of the nucleus is just as complex as the cytoplasm of the cell, the only difference being that, in contrast to the cytoplasm, the functional compartments within the nucleus are not individually enclosed by membranes, and so are not visible when the cell is observed using conventional light or el

4、ectron microscopy techniques. Each chromosome has its own territory within the nucleusEach chromosome has its own territory within the nucleusEach chromosome has its own territory within the nucleusEach chromosome comprises a series of topologically associated domainsInsulators mark the boundaries o

5、f topologically associated domains Insulator sequences in the fruit fly genomeInsulators mark the boundaries of topologically associated domains Loop formation at insulator sitesKrivega M, Dean A: Insulators Organize Chromatin: Emerging Rules of the Game. Mol Cell 2011, 44:1-2.Wood AshleyM, VanBortl

6、e K, Ramos E, Takenaka N, Rohrbaugh M, Jones BrianC, Jones KeithC, Corces VictorG: Regulation of Chromatin Organization and Inducible Gene Expression by a Drosophila Insulator. Mol Cell 2011, 44:29-38.10.2 Chromatin modifications and genome expressionPositions at which acetyl groups are attached to

7、lysines within the N-terminal regions of the four core histones.Histone deacetylation represses active regions of the genome Positions where modifications occur in four core histonesThe pattern of histone H3 modification is linked to gene activity.DNase I hypersensitive sites upstream of the human b

8、eta-globin gene cluster.Additional hypersensitive sites are seen immediately upstream of each gene. These sites are specific to different developmental stages and are seen only during the phase of development when the adjacent gene is active.10.3 DNA modification and genome expressionMaking chemical

9、 changes to the DNA, semipermanent silencing.The modified state is inherited in cell division.Both maintenance and de novo methylation result in repression of gene activity.Methyl-CpG-binding proteins (MeCPs) are components of the Sin3 and NuRD histone deacetylase complex.Methylation of the CpG isla

10、nd upstream of a gene provides recognition signals for the MeCP components of a histone deacetylase complex (HDAC). The HDAC modifies the chromatin in the region of the CpG island and hence inactivates the gene.Methylation is involved in genomic imprinting and X activationImprinting genes tend to oc

11、cur in clusters.Igf2, a growth factor gene.H19 geneEvolutionary conflicts between the males and females.David Haig, Professor of Biology in Harvard universityX activationBarr body.Some 20% genes escape the process and remain functional.X inactivation center (Xic), Xist, transcribed into 25 kb noncod

12、ing RNA.Replacement of histone H2A, one of the members of the core octamer of the nucleosome (Section 2.2.1), with a special histone, macroH2A1 Deacetylation of histone H4, as usually occurs in heterochromatin; Hypermethylation of certain DNA sequences, although this appears to occur after the inact

13、ive state has been set up. Discussion and speculationNiu DK and Wang YF (1995). Why animals have tumours. Acta Biotheoretica 43: 279-280. 我的作業(yè)。Further ReadingBuratowski, S., and D. Moazed. 2005. Gene regulation: Expression and silencing coupled. Nature 435:1174-1175.Haig, D. 2004 Genomic imprinting and kinship: how good is the evidence? Annual Review of Genetics 38: 553-585.Prendergast et al. 2007. Chromatin st