[医学]5 真核基因表达调控.ppt

Eukaryotic Gene Expression Managing the Complexities of Controlling Eukaryotic Genes Logical Expression Control Points (1) DNA packaging (2) Transcription (3) RNA processing (4) mRNA Export (5) mRNA masking/unmasking and/or modification (6) mRNA degradation (7) Translation (8) Protein modification (9) Protein transport (10) Protein degradation Control of Gene Expression Eukaryotes Have Large Complex Geneomes The human genome is about 3 x 109 base pairs or ≈ 1 m of DNA. Because humans are diploid, each nucleus contains 6 3 x 109 base pairs or ≈ 2 m of DNA. That is a lot to pack into a little nucleus! Eukaryotic DNA Must be Packaged Eukaryotic DNA exhibits many levels of packaging. The fundamental unit is the nucleosome, and DNA wound around histone proteins. Nucleosomes arrange themselves together to form higher and higher levels of packaging. Packaging DNA: Levels of Eukaryotic Chromatin Structure Highly Packaged DNA Cannot be Expressed (1) The most highly packaged form of DNA is “heterochromatin”. (2) Heterochromatin cannot be transcribed, therefore expression of genes is prevented. (3) Chromosome puffs (胀泡) on some insect chomosomes illustrate where active gene expression is going on. Transcriptional Regulation: Effects of Chromatin Structure  Decompaction of chromatin: Transcription factors unwind nucleosomes in the area where transcription will begin, creating  DNAse I hypersensitive sites. RNA polymerase unwinds more nucleosomes as transcription  proceeds. Transcriptional Regulation: Effects of Chromatin Structure  Transcriptional Regulation: Effects of Chromatin Structure Eukaryotic RNA Polymerase II Eukaryotic RNA Polymerase II Promoters Eukaryotic RNA Polymerase II Promoters A “Simple” Eukaryotic Gene Response Elements (1) Response elements are short sequences found either within about 200 bp of the transcription start site, or as part of enhancers. (2) Different genes have different response elements. (3) Binding of transcription factors