Gene Transcription
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Introduction
Gene transcription is responsible for the specific expression of the various proteins in a cell, in response to upstream signals mediated largely by transcription factors. RNA is transcribed from DNA templates by RNA polymerases, with the RNA being identical to the nontemplate, coding strand.
Start of Transcription
Promoters and enhancers act as binding sites for general transcription factors, which include CTF, SP1, and TFIID. Once in place, these transcription factors recruit RNA Pol II to the transcription start site.
Transcription factors are specific proteins that interact with DNA and other transcription factors in order to control gene expression, either positively or negatively.
The nuclear receptor superfamily act in the nucleus by binding to hormone responsive elements (HREs) in the enhancer regions of specific genes, thus activating transcription. Ligands of the superfamily include steroid hormones, vitamin D, thyroid hormone, and retinoic acid. Ligands can bind in the cytoplasm or the nucleus.
Nuclear receptor coregulators include coactivators or corepressors that facilitate or inhibit interaction with the basal transcription complex.
CBP/p300 contains histone acetyltransferase activity and influences chromatin remodeling.
SRC-1 enhances transcription.
NCoR (Nuclear receptor co-Repressor) inhibits transcription.
Intracellular signaling cascades influence the activity of various transcription factors. For example, glucagon signals through cAMP and PKA to phosphorylate and activate the TF CREB. Insulin activates the MAPK cascade, resulting in the phosphorylation of AP-1.
Promoters, Enhancers, and Repressors
The promoter is the beginning of the DNA sequence to be transcribed. Approximately 25 bases upstream of the transcription start site is the TATA box, and 70-80 bases upstream of the start site is the CAAT box.
Enhancers can be upstream or downstream of the promoter and can be found up to 2000 bp away. Enhancers contain responsive elements that bind trans factors called activators.
RNA Polymerases
There are three distinct eukaryotic polymerases.
RNA Pol I synthesizes the large rRNAs in the nucleolus.
RNA Pol II synthesizes precursor mRNAs. RNA Pol II is inhibited by amanitin, a toxin from the mushroom Amanita phalloides (death cap or destroying angel)
RNA Pol III produces small RNAs, including tRNAs and some snRNAs.
Chromatin and Control of Transcription
Transcription is tightly controlled by various factors.
Most actively transcribed genes are found in euchromatin, which is more relaxed that the highly condensed heterochromatin.
Methylated DNA is more resistant to transcription. In each female cell, one of the X chromosomes is methylated and therefore inactivated.
Histone acetylation allows for unwinding of DNA and facilitates active transcription.
Inhibitors of Transcription
As mentioned, RNA Pol II is inhibited by amanitin, a toxin from the mushroom Amanita phalloides (death cap or destroying angel).
Rifampin is a selective prokaryotic RNA Pol inhibitor that works by changing its conformation.
Actinomycin D binds DNA and inhibits RNA Pol movement.
Cordycepin is a nucleoside analogue, preventing chain termination.
Resources and References
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