* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Some transcription factors ("Enhancer
Non-coding RNA wikipedia , lookup
Secreted frizzled-related protein 1 wikipedia , lookup
Epitranscriptome wikipedia , lookup
Genomic imprinting wikipedia , lookup
Histone acetylation and deacetylation wikipedia , lookup
List of types of proteins wikipedia , lookup
Transcription factor wikipedia , lookup
RNA polymerase II holoenzyme wikipedia , lookup
Molecular evolution wikipedia , lookup
Non-coding DNA wikipedia , lookup
Community fingerprinting wikipedia , lookup
Genome evolution wikipedia , lookup
Eukaryotic transcription wikipedia , lookup
Gene expression profiling wikipedia , lookup
Gene nomenclature wikipedia , lookup
Point mutation wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Gene desert wikipedia , lookup
Gene expression wikipedia , lookup
Endogenous retrovirus wikipedia , lookup
Gene regulatory network wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Promoter (genetics) wikipedia , lookup
Lecture 7. Regulation of Eukaryotic Gene Expression 1. Eukaryotic Gene structure A gene is the DNA sequence composed of several regions of distinct function for coding the synthesis of RNA or polypeptide. There are coding and non coding regions in the DNA associated with genes: The non coding regions include controlling regions (promoters and transcriptional regulatory sequences), introns and polyadenylation signals. Coding regions (open reading frame) include exons sequences to be translated. Controlling regions determine the pattern of expression of a particular gene in a particular cell type. Specifically, the promoter dictates where transcription starts and is located just upstream of that site. Enhancers influence the level of transcription as well as the cell-type specificity. Enhancers can be located at varying distances and upstream, within, or downstream, of the genes they control. The portions of the gene that encode the amino acid sequence of a protein are called the exons. These protein-coding regions can be interrupted by intervening sequences, or introns. Introns can vary in number from 0 to as many as 80 per gene. Fig.14. Eukaryotic gene structure. II. DNA sequences of eukaryotic protein-coding gene 1) The usual linear order for DNA sequences at a gene is: a) Regulatory element(s) (where activators or suppressors bind); b) promoter region (where the RNA polymerase complex binds); c) transcription start site (in 5' UTR); d) exon(s); e) introns (between exons, 5'GT and 3'AG, variable number); f) 3' UTR consisting of a translation stop codon (TAA, TGA, or TAG); g) AATAAA polyadenylation signal; and the site for addition of poly A tail. DNA sequences of gene Feature Description Promoters TATA-box (-25); many genes have a GC rich region upstream of (and often including) the first exon. Unlike the rest of the genome, it has no deficit of the dinucleotide CpG. Exons These are the parts of the gene which will remain in the mRNA after the primary transcript is processed. Introns These parts of the gene which are removed from the primary transcripts by splicing translated region This is the region of the gene which codes for protein (exons). 5'UTR The region of exon 1 between the cap site and the start of translation at the first AUG codon. 3'UTR The region of the final exon between the translation stop codon and the polyA addition site at the end of the transcript. 2) Enhancers Some transcription factors ("Enhancer-binding protein") bind to regions of DNA that are thousands of base pairs away from the gene they control. They are named Enhancers. Enhancers can be located upstream, downstream, or even within the gene they control. Binding the transcription factors with enhancer increases the rate of transcription of the gene. Enhancer-binding proteins have sites that bind to transcription factors ("TF") assembled at the promoter of the gene. This would draw the DNA into a loop: 3) Silencers Silencers are control regions of DNA that may be located thousands of base pairs away from the gene they control. However, when transcription factors bind to them, expression of the gene they control is repressed. 4) Hormones exert many of their effects by forming transcription factors The complexes of hormones with their receptor represent one class of transcription factor. Hormone "response elements", to which the complex binds, are promoter sites. Embryonic development requires the coordinated production and distribution of transcription factors. 5) Insulators are stretches of DNA (as few as 42 base pairs) located between the o enhancer(s) and promoter or o silencer(s) and promoter of adjacent genes o The insulator prevents a gene from being influenced by the activation (or repression) of its neighbors. There is an insulator between the alpha gene promoter and the delta gene promoter that ensures that activation of one does not spread over to the other. Fig. 15. The enhancer for the promoter of the gene for the delta chain of the gamma/delta T-cell receptor for antigen (TCR) is located close to the promoter for the alpha chain of the alpha/beta TCR (on chromosome 14 in humans). There is an insulator between the alpha gene promoter (Pα) and the delta gene promoter (Pδ). T - cell must choose between one or the other. All insulators discovered so far in vertebrates work only when bound by a protein designated CTCF ("CCCTC binding factor"; named for a nucleotide sequence found in all insulators). CTCF has 11 zinc fingers. III. Other mechanisms for regulation of eukaryotic gene expression 1) Methylation. Example: In mammals (mice, humans, pigs), only the allele for insulin-like growth factor-2 (IGF2) inherited from one's father is active; that inherited from the mother is not — a phenomenon called imprinting. The mechanism: the mother's allele has an insulator between the IGF2 promoter and enhancer. So does the father's allele, but in his case, the insulator has been methylated. CTCF can no longer bind to the insulator, and so the enhancer is now free to turn on the father's IGF2 promoter. 2) Alternative Splicing is exon skipping and splicing of mRNA to make more than one protein from a single gene. Some genes have alternate splice sites so that several different proteins can be produced from the multiple mRNAs that are produced from the same gene. The ability to make more than one gene product (polypeptide) from a single gene explains in part how we can have many more gene products than only the number of genes sequenced in the Human Genome project. 3) Post transcriptional processes that modify the initial RNA transcript usually include 5' cap addition, 3' poly A addition, and alternative splicing of introns to form different mRNAs from the same gene. The use of alternative promoters is common and is used to generate cell type specific mRNAs. These alternative promoters may be found within introns of the gene. The human dystrophin (DMD) gene which has more than 79 exons has at least eight different alternative promoters. 4) Post translational cleavage of proteins, while rare, can also occur as in the case of insulin and some hormones. Many different genes and many different types of cells share the same transcription factors — not only those that bind at the basal promoter but even some of those that bind upstream. The unique combination of promoter sites and the transcription factors that are chosen is the main type of regulation of eukaryotic genes.