Transcription第九
- 格式：pdf
- 大小：4.67 MB
- 文档页数：92
Chromatin/chromosome Example: Globin expression Nucleosome Epigenetics A. Histone modifications/variants B. DNA methylation C. Regulatory non-coding RNAs
Felsenfeld & Groudine, Nature, 2003
Chromatin Silence Transcription
Position effect Condensation effect
Position effect
heritable
n effect variegation (PEV)
Chromatin/chromosome
History Structure Chromatin Silence Transcription Superhelical Tension Kissing chromosomes Chromosomal dosage and compensation
When deleted, the beta-globin gene in the
erythroid cells remains DNaseI resistant. When inserted, the LCR and gene in one part promises a high levels of expression.
Condensation effect
Highly condensed chromatin can prevent gene
expression Use DnaseI to research Example: globin expression
Globin Expression
Locus control region (LCR)
Chromatin remodeling Histone modification
General transcription factor
Activate Chromatin
Three models proposed to explain the long-range influence of a locus control region (LCR) on gene activity. Each model proposes a different function for the LCR site. The actual mechanism that causes long-range effects is unknown, and other mechanisms are also conceivable.
Transcription Control of Gene Expression Ⅲ
Chromatin/chromosome Example: Globin expression Nucleosome Epigenetics A. Histone modifications/variants B. DNA methylation C. Regulatory non-coding RNAs
Chromatin history
Walther Flemming – Coined term “chromatin” in 1880 – Described mitosis Subsequent work revealed that
chromatin is composed of nucleic acid and protein Histones package to form chromatin in 1990
Transcription Control of Gene Expression Ⅲ
Chromatin/chromosome Example: Globin expression Nucleosome Epigenetics A. Histone modifications/variants B. DNA methylation C. Regulatory non-coding RNAs
Chromatin/chromosome
History Structure Chromatin Silence Transcription Superhelical Tension Kissing chromosomes Chromosomal dosage and compensation
Dimitris Kioussis Nature 435, 579-580 (2 June 2005) | doi: 10.1038/435579a
The three dimensions of gene regulation
a, Linear view of gene regulation. b, The 'looping-scanning' model of gene regulation. c, Gene regulation in 3D. Spilianakis et al. find that genes from different chromosomes (A and B) are in close proximity until a developmental signal stimulates the cells, when the genes split apart. One moves to a region that represses gene expression (heterochromatin, red) and the other relocates to an area with many active genes (euchromatin, green). d, Genes from different chromosomes might come into contact when the chromatin containing them loops out from their chromosome 'territory'.
Model for the control of the human beta-globin gene. CP1 are found in many types of cells; GATA-1, are present in only a few types of cells including red blood cells and therefore are thought to contribute to the cell-type specificity of beta-globin gene expression. As indicated by the double-headed arrows, several of the binding sites for GATA-1 overlap those of other gene regulatory proteins; it is thought that occupancy of these sites by GATA-1 excludes binding of other proteins. (Adapted from B. Emerson, In Gene Expression: General and Cell-Type-Specific [M. Karin, ed.], pp. 116-161. Boston: Birkhauser, 1993.)
Kissing chromosomes
A three-dimensional examination of gene regulation suggests that portions from different chromosomes 'communicate' with each other, and bring related genes together in the nucleus to coordinate their expression.
Superhelical Tension
Superhelical tension in DNA causes DNA
supercoiling
Superhelical tension in DNA causes DNA supercoiling (positive supercoil)
Superhelical Tension
X-inactivation
The repressed X-chromosome condenses to form a Barr body In fact, 10-15% of repressed alleles are active – to compensate for recessive alleles of sex-linked disorders including haemophilia and colour blindness
Transcription Control of Gene Expression Ⅲ
Group 9 2006.11.22
Gene expression can be controlled in different levels
Transcription Control of Gene Expression Ⅲ
Chromosomal dosage and compensation
Mary Lyon – 1961 in cells with multiple X chromosomes, all but one is inactivated during mammalian embryogenesis – the “Lyon effect” X-inactivation; which X? Usually random … but always paternal in marsupials and variable in calico cats representing regional expression of differing pigmentation genes on alternate X chromosomes
