Regulación de la expresión génica
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1. The document describes the process of chromatin remodeling from a loose structure to a highly condensed structure. It progresses from nucleosomes forming a beads-on-a-string structure, to a 30nm fiber, then loops and folds to form a metaphase chromosome hundreds of nanometers in length. 2. It explains how histone acetylation promotes a loose chromatin structure allowing transcription, while unacetylated histones result in a tighter structure preventing transcription. 3. The stages of gene expression are outlined, from transcription to RNA processing and export from the nucleus for translation into protein in the cytoplasm.
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Regulación de la expresión génica
- 1. Figure 19-01
- 12. LE 19-2 DNA double helix Histone tails His- tones Linker DNA (“string”) Nucleosome (“bead”) 10 nm 2 nm Histone H1 Nucleosomes (10 nm fiber) 30 nm Nucleosome 30-nm fiber 300 nm Loops Scaffold Protein scaffold Looped domains (300-nm fiber) Metaphase chromosome 700 nm 1,400 nm
- 13. LE 19-2a DNA double helix Histone tails His- tones Linker DNA (“string”) Nucleosome (“bead”) 10 nm 2 nm Histone H1 Nucleosomes (10-nm fiber)
- 14. LE 19-2b 30 nm Nucleosome 30-nm fiber
- 15. LE 19-2c 300 nm Loops Scaffold Protein scaffold Looped domains (300-nm fiber)
- 16. LE 19-2d Metaphase chromosome 700 nm 1,400 nm
- 17. LE 19-3 Signal NUCLEUS DNA RNA Chromatin Gene available for transcription Gene Exon Intro Transcription Primary transcript RNA processing Cap Tail mRNA in nucleus Transport to cytoplasm CYTOPLASM mRNA in cytoplasm Translation Degradation of mRNA Polypeptide Cleavage Chemical modification Transport to cellular destination Degradation of protein Active protein Degraded protein Chromatin modification: DNA unpacking involving histone acetylation and DNA demethylation
- 18. LE 19-4 Histone tails Amino acids available for chemical modification DNA double helix Histone tails protrude outward from a nucleosome Acetylation of histone tails promotes loose chromatin structure that permits transcription Unacetylated histones Acetylated histones
- 19. LE 19-4a Histone tails Amino acids available for chemical modification DNA double helix Histone tails protrude outward from a nucleosome
- 20. LE 19-4b Acetylation of histone tails promotes loose chromatin structure that permits transcription Unacetylated histones Acetylated histones
- 22. LE 19-5 Enhancer (distal control elements) Proximal control elements Upstream DNA Promoter Exon Intron Exon Intron Exon Downstream Transcription Poly-A signal sequence Termination region Intron Exon Intron Exon RNA processing: Cap and tail added; introns excised and exons spliced together Poly-A signal Cleaved 3′ end of primary transcript 3′ Poly-A tail 3′ UTR (untranslated region) 5′ UTR (untranslated region) Start codon Stop codon Coding segment Intron RNA 5′ Cap mRNA Primary RNA transcript (pre-mRNA) 5′ Exon
- 23. LE 19-6 Distal control element Activators Enhancer DNA DNA-bending protein TATA box Promoter Gene General transcription factors Group of mediator proteins RNA polymerase II RNA polymerase II RNA synthesis Transcription Initiation complex
- 24. LE 19-7 Control elements Enhancer Promoter Albumin gene Crystallin gene Available activators Available activators Albumin gene not expressed Albumin gene expressed Liver cell Lens cell Crystallin gene not expressed Crystallin gene expressed Liver cell nucleus Lens cell nucleus
- 26. LE 19-9 Dicer Hydrogen bond Protein complex miRNA Target mRNA Degradation of mRNA OR Blockage of translation
- 27. LE 19-10 Protein to be degraded Ubiquitinated protein Proteasome Protein entering a proteasome Protein fragments (peptides) Proteasome and ubiquitin to be recycled Ubiquitin
- 28. LE 19-11 Proto-oncogene DNA Translocation or transposition: gene moved to new locus, under new controls New promoter Gene amplification: multiple copies of the gene Point mutation within a control element Oncogene Oncogene Point mutation within the gene Normal growth-stimulating protein in excess Normal growth-stimulating protein in excess Normal growth-stimulating protein in excess Hyperactive or degradation- resistant protein
- 29. LE 19-12_1 Cell cycle-stimulating pathway Growth factor G protein Receptor MUTATION Protein kinases (phosphorylation cascade) NUCLEUS Hyperactive Ras protein (product of oncogene issues signals on its own. Transcription factor (activator) DNA Gene expression Protein that stimulates the cell cycle
- 30. LE 19-12_2 Active form of p53 DNA DNA damage in genome UV light Protein kinases MUTATION Defective or missing transcription factor, such as p53, cannot activate transcription Protein kinases (phosphorylation cascade) Cell cycle-inhibiting pathway Cell cycle-stimulating pathway Protein that stimulates the cell cycle NUCLEUS DNA Gene expression Transcription factor (activator) Receptor G protein Growth factor MUTATION Hyperactive Ras protein (product of oncogene) issues signals on its own Protein that inhibits the cell cycle
- 31. LE 19-12_3 Protein overexpressed EFFECTS OF MUTATIONS Protein absent Cell cycle not inhibited Increased cell division Cell cycle overstimulate Effects of mutations Active form of p53 DNA DNA damage in genome UV light Protein kinases MUTATION Defective or missing transcription factor, such as p53, cannot activate transcription Protein kinases (phosphorylation cascade) Cell cycle-inhibiting pathway Cell cycle-stimulating pathway Protein that inhibits the cell cycle NUCLEUS DNA Gene expression Transcription factor (activator) Receptor G protein Growth factor MUTATION Hyperactive Ras protein (product of oncogene) issues signals on its own Protein that stimulates the cell cycle
- 32. LE 19-13 Colon Colon wall Loss of tumor- suppressor gene APC (or other) Normal colon epithelial cells Small benign growth (polyp) Larger benign growth (adenoma) Activation of ras oncogene Loss of tumor- suppressor gene DCC Loss of tumor- suppressor gene p53 Additional mutations Malignant tumor (carcinoma)
- 33. LE 19-14 Exons (regions of genes coding for protein, rRNA, or tRNA) (1.5%) Alu elements (10%) Simple sequence DNA (3%) Large-segment duplications (5–6%) Unique noncoding DNA (15%) Introns and regulatory sequences (24%) Repetitive DNA that includes transposable elements and related sequences (44%) Repetitive DNA unrelated to transposable elements (about 15%)
- 34. Figure 19-15
- 35. LE 19-16 DNA of genome Transposon is copied Mobile transposon Transposon Insertion New copy of transposon Transposon movement (“copy-and-paste” mechanism) Retrotransposon movement DNA of genome Insertion RNA Reverse transcriptase Retrotransposon New copy of retrotransposon
- 36. LE 19-16a DNA of genome Transposon is copied Mobile transposon Transposon Insertion New copy of transposon Transposon movement (“copy-and-paste” mechanism)
- 37. LE 19-16b Retrotransposon movement DNA of genome Insertion RNA Reverse transcriptase Retrotransposon New copy of retrotransposon
- 38. LE 19-17 DNA Non-transcribed spacer RNA transcripts Transcription unit DNA 18S 5.8S 28S rRNA 18S 5.8S 28S Part of the ribosomal RNA gene family Heme Hemoglobin α-Globin β-Globin α-Globin gene family β-Globin gene family Chromosome 11Chromosome 16 ζ ψζ ψα2 ψα1 α1α2 ψβ δ βGγ∍ Aγ Embryo Embryo Fetus Adult Fetus and adult The human α-golbin and β-globin gene families
- 39. LE 19-17a DNA Non-transcribed spacer RNA transcripts Transcription unit DNA 18S 5.8S 28S rRNA 18S 5.8S 28S Part of the ribosomal RNA gene family
- 40. LE 19-17b Heme Hemoglobin α-Globin β-Globin α-Globin gene family β-Globin gene family Chromosome 11Chromosome 16 ζ ψζ ψα2 ψα1 α1α2 ψβ δ βGγ ∍ Aγ Embryo Embryo Fetus Adult Fetus and adult The human α-globin and β-globin gene families
- 41. LE 19-18 Nonsister chromatids Transposable element Gene Crossover Incorrect pairing of two homologues during meiosis and
- 42. LE 19-19 Duplication of ancestral gene Mutation in both copies Transposition to different chromosomes Further duplications and mutations Ancestral globin gene ζ ψζ ψα2 ψα1 α1α2 ψβ δ βGγ∍ Aγ α-Globin gene family on chromosome 16 ψϑ β-Globin gene family on chromosome 11 ζ α α α β β ∍ βγ Evolutionarytime
- 43. Table 19-1
- 44. LE 19-20 Epidermal growth factor gene with multiple EGF exons (green) EGF EGF EGF EGF F F F F Fibronectin gene with multiple “finger” exons (orange) K K KEGFF Plasminogen gene with a “kringle” exon (blue) Portions of ancestral genes TPA gene as it exists today Exon shuffling Exon shuffling Exon duplication
Notas del editor
- Estructura del operón.
- Estructura del operón triptófano
- Regulación positiva. La proteína CAP es una proteína reguladora que activa genes catabólicos). Cuando hay glucosa en E.coli los niveles de AMPc son bajos y el complejo CAP-AMPc no se forma. Cuando la glucosa se agota, aumentan los niveles de AMPc y se forma el complejo CAP-AMPc uniéndose al promotor, permitiendo la transcripción.
- Silenciamiento del ARN: ARNi micro ARN: ARNss de 21 a 25 nucleótidos con capacidad de regular la trasncripción por interferencia al unirse por complementariedad a ARNm bloqueando la transcripción o permitiendo la degradación del ARNm. Tienen una importante función en la defensa contra la invasión de los virus y en el silenciamiento de los transposones. ARNmi: 19 a 14 nucleótidos bloqueando la traducción
- regulación post-traduccional.
- Barbara McClintock y los transposones. Maíz con variaciones en la pigmentación por causa de elementos transponibles