Regulation of Gene Expression in Eukaryotes (Initiation of Transcription…
Regulation of Gene Expression in Eukaryotes
Initiation of Transcription (MOST IMPORTANT)
a. General (basal) Transcription factors
Specific Transcription Factors
Heterochromatin- Trnascriptionally inactive bcuz the histones are blocking the DNA which is tightly condensed. Darkly stained
Eucrhomatin- Transcriptionally active since the DNA is not tightly coiled forming the secondary packaging stage. (nuclesome formation)
Revealed by DNase 1 Hypersensitivity experiments that it easily degrades euchromatin than heterochromatin. Histones inhibit transcription but can be modified (methylated (inactive regions of genome) or acetylated(active regions of genome))
Epigenetic Control ( Activate and deactivate genes)
Methylation of DNA or Histones
DNA- CpG Islands which differ in cell types Inactive X-Chromosome in female cats (Barr Body)
Epigenetic inheritance the methylated DNA or Histones is passed down to the offspring from the parent . Eg: Nuturing Behaviour in Mice.
mRNA has different half lives based on genes from which it is transcribed and tissue it will be expressed in and is subjected to degradation. .
Maybe be cleaved by Small Interfering RNA (siRNA) or microRNA. This is reffered to as RNA Interference RNAi, which silences genes.
snRNA degrades mRNA b4 Translation by binding to RNA-Induced Splicing Complex (RISC) separating the RNA strand into a Passenger-strand ( degraded) and Guide Strand (cleaved and not translated)
microRNA bind to complementary RNA to prevent translation . This production begins in the nucleus and ends in the cytoplasm, and are from regions of RNA Transcirpt that fold back on themselves to form short hairpin loops. miRNA loads into RISC which targets gene that are complementary to the miRNA sequence. This may be imperfecct and therefore inhibits translation.
Out of the nucleus is regulated by special proteins. mRNA must be in the cytoplasm for the gene to be expressed. Experiments show that half of the mRNA never leaves the nucleus and is degraded.
If protein is not stable it will be degraded and once degraded it will not be expressed.
Hormonal Control of Gene Expression (mechanism of regulating transcription in response to demands of the environment)
Only target cells with hormone specifc receptors maintained by a feedback pathway. 2 pathways of delivering the hormonal signal
Steroid Hormones: through the cell membrane and bind to receptors (nucleus cytoplasm and plasma membrane) which then moves to the nucleus and bind directly to the DNA (initiation factor) and regulate gene expression. Eg: Mammalian: Estrogen and Testosterone- Small molecules
Polypeptide Hormones: bind to the cell surface and activate the transmembrane enzymes to produce second messenger (CAMP)which transduces a signal to the nucleus. This then activates the gene transcription. EG: Insulin (doesnt enter the cell due to large size)
Post Transnational modifications / Regulations
Proteins to be degraded are markes with ubiquitin (small regulatory proetin) this binds to the protine and its interactions are altered via the proteasome.