From prokaryotic to eukaryotic gene regulation, and beyond Flashcards
How is gene regulation in eukaryotes different?
- There are no operons.
- Transcription is separated from translation.
- There is a bewildering array of regulatory proteins.
- RNA transcripts are frequently processed (spliced).
- Chromatin affects expression
What is ENCODE?
Encyclopaedia Of DNA Elements
- a public research project which aims to identify functional elements in the human genome
- A catalogue of ANY biochemical activity associated with each nucleotide in the human genome 2012
- FROM SEQUENCE TO FUNCTION:
- 2-Dimensional TO 3/4-Dimensional
What is the role of ENCODE?
- Map RNA transcripts, binding sites for transcription factors and chromosomal proteins.
- Identify all protein-coding genes.
- Identify promoters and enhancers with transfection of reporter constructs into cell lines
What has ENCODE identified so far?
• 1.5%of the genome actually contains instructions for making proteins.
• 20% are sites where proteins stick to DNAswitching genes on or off.
• 50% of sequences are involved in DNA packaging, encode non-coding RNAs and introns.
+SNPs – variants at specific DNA letters—that correlate with the risk of different conditions.
-Disease-associated SNPs are 60 percent of more likely to lie within functional, noncoding regions, especially in promoters and enhancers.
-The team found five SNPs associated with Crohn’s disease, a type of bowel disorder. that interacted with a specific type of transciption factor.
What importance does the architecture of the genome have?
-THE GENOME HAS A COMPLEX BIOLOGICALY RELEVANT 3-D ARCHITECTURE.
+1,000 sequences were switches in one part of the genome which were physically reaching over and controlling the activity of a distant gene
What are Epigenetics?
- Inherited DNA context
- “Epigenetics” refers to covalent modification of DNA, protein, or RNA, resulting in changes to the function and/or regulation of these molecules, without altering their primary sequences.
- In some cases, epigenetic modifications are stable and passed on to future generations, but in other instances they are dynamic and change in response to environmental stimuli.
How can DNA expression be altered?
-can be switched of by histones (histone methylation)
+by encompassing their tails around the DNA, thereby restricting access to the DNA.
-MicroRNAs also alter Expression
+They generally bind to the 3’-UTR (untranslated region) of their target mRNAs and repress protein production by destabilizing the mRNA and translational silencing.
What is an agouti mutation?
- Agouti (gene) agouti is a gene that controls the distribution of the natural pigment, melanin, in the hair of mammals and helps determine their coat color patterns
- in rats agouti mutation means lighter hair color, so yellow instead of brown, but is associated with lethal obesity
- This phenotype is the result of methylation not happening as in regular rats the agouti gene is turned off by methylation and in agouti rats the gene is not methylated producing agouti through all of the rats life.
In the future, which other features of chromosomes will
become increasingly important?
• Chemical modification of bases
– Understand DNA methylation now
– Others may be discovered
• Interaction of various proteins with chromosome
• Three dimensional structure of proteins in nucleus
– May determine interactions of chromosomal regions with regions of nuclear envelope.
• More effective tools need to be developed to examine chromosome features
