Transcription and Disease

In this post I will be discussing how promoters, enhancers, transcription factors and RNA polymerase interact to transcribe DNA into RNA. I'll also be discussing a disease caused by either a defective transcription factor or a defective promoter. 

Transcription:

Transcription is the process in which the genetic information on DNA is transferred to a messenger RNA (mRNA) molecule. The DNA molecule is 'opened up' by RNA polymerase allowing a complimentary mRNA molecule to be made from the strand of DNA. For every adenine (A) nucleotide on the DNA molecule, a uracil (U) nucleotide is added to the mRNA. For every guanine (G), cytosine (C) and thymine (T) on the DNA strand, a C, G and A nucleotide is added to the mRNA molecule respectively. The sequence of nucleotides on the DNA molecule is termed the genetic code. 

In order for transcription to occur the cell needs:

• Promoters
• Enhancers or Silencers
• Transcription factors
• and RNA polymerase (RNAP)

Promoters:

Promoters are DNA sequences located upstream of a gene that direct and define where and in what direction transcription is to commence. They consist of a short sequence of elements, for example the CAAT-box, the TATA-box, or the GC-box. Promoters bind RNAP and transcription factors. Promoters must bind to transcription factors in order for them to work and they are unique to each gene. 

Enhancers:

Enhancers are regions of DNA which determine how frequently and when transcription occurs. They bind to specific transcription factors or enhancer DNA binding proteins and elevate the rate of transcription initiation. Enhancers can be found long distances away from promoters and can be either upstream or downstream from the start site of transcription. The binding of transcription factors to enhancers increases the rate of transcription, this is known as transcription synergy. When several transcription factors are bound to the enhancer sequences upstream of the promoter, the increase in transcription rate is higher than that expected from an additive effect.

Silencers: 

Silencers are DNA sequences that a repressor protein binds to and causes an inhibition of transcription. 

 Transcription Factors:

Transcription factors are proteins that bind to the promoter and to RNAP to switch on protein synthesis. Transcription factors have at least 2 domains:

• An activation domain: interacts with the components of RNAP and with other regulatory proteins, effecting the efficiency of DNA binding.
• DNA binding domain: this consists of amino acids that recognise specific DNA bases near the start of transcription.

Transcription factors "recognise" specific segments of DNA in the major and minor grooves and interact with them via hydrogen bonds, ionic bonds and hydrophobic forces. Transcription factors have different structural motifs, eg. the zinc finger, helix-turn-helix, and Leucine zipper. 

 RNA Polymerase:

RNAP doesn't need an RNA primer and recognises and binds to promoter sequences. RNAP 'opens' a short segment of DNA which then binds the initiating triphosphate during the formation of mRNA from DNA.

Transcription Factors and Disease:

An example of a disease which results from problems with a transcription factor is Pituitary Dwarfism. Pituitary Dwarfism is caused by a mutation in the Pit 1 transcription factor. Pit 1 activates the transcription of Growth Hormone in the body. The mutation prevents Pit 1 from binding to the promoter which prevents the production of Growth Hormone. 

And that's it :)