Special transcription factors

TATA box연구를 통해 DNA의 탄성도가 A, T 염기의 비율에 따른 유의미하게 변화한다고 주장하였는데요. 이러한 결과는 진핵세포의 전사조절 기전에 대한 이해와 함께 그 중요성을 인정받을 수 있다고 생각합니다.

 

Transcription factors that regulate transcription include general transcription factors (GTFs) used for direct transcription and special transcription factors (STFs) that control the level of gene expression. As a mechanism that regulates transcription, in the interaction between the mediator complex and activators that bind to various regulatory sequences on DNA, the activators belong to special transcription factors. A sequence that promotes the transcription of a specific gene present in DNA is generally referred to as an enhancer. As opposed to an amplifier, a sequence that inhibits gene transcription is called an insulator, and although these regulatory sequences have been described above, some are very far from the gene location.

 

증폭자와 같은 전사 촉진 서열에 결합하는 단백질만 활성인자라 부르고, 절연인자를 비롯한 전사 억제 서열에 결합하는 단백질은 억제인자(Repressor)라 구별하는 논문들도 있습니다.

 

 

Activators have a DNA binding site and an activation site in common, and activate transcription by attracting transcriptional machinery to a specific gene. These include not only proteins directly involved in transcription, but also histone acetyltransferases (HATs) and nucleosome remodeling enzymes. Inhibitors directly interfere with the binding of the activator to the enhancer, or prevent the activator bound to the enhancer from interacting with the mediator complex. Alternatively, transcription is inhibited by attracting histone deacetylases (HDATs, Histone deacetyltransferases) or histone methylation transferases (HMTs, Histone methyltransferases). In particular, histone methylation or DNA methylation by DNA methyltransferases (DMTs, DNA methyltransferases) results in gene silencing, which can permanently turn off gene activity.

 

 

An activator is clearly divided into subunits with a DNA binding site and an activation site, and a new type of activator can be created by appropriately combining exons. This means that the DNA binding site of activator A and the activation site of activator B can be recombined. The most well-studied activator is the activator Gal4. This protein activates the Lac operon in yeast to promote the expression of the lacZ gene. Therefore, when cultured in a medium containing X-gal, the yeast in which Gal4 is normally expressed has a blue color. As an experiment using Gal4, there is an experiment that artificially replaces the DNA binding site with the DNA binding site of a protein called LexA, a bacterial suppressor. In the yeast DNA, the UASG (Upstream activating sequence for GAL), which originally binds to Gal4, was cut, and the site to which LexA binds was replaced. As a result, it was confirmed that the Gal4-LexA hybrid protein was normally bound to the LexA binding site, and the Lac operon was also normally expressed.

 

이는 DNA 결합부위와 활성화 부위가 functinally하게 구분된다는 것을 의미합니다.

 

 

The DNA binding sites of these activators have a fairly standardized form, and usually bind as a dimer. Most bacteria form homodimers, but eukaryotes form heterodimers, or monomers are combined with the help of helper proteins.

 

Helix-turn-helix motif : a method mainly used by bacteria and also used by eukaryotes

The spiral-turn-helix motif includes the Homeodomain. Many DNA binding proteins have a homeodomain. It has three α helix structure, and one α helix is ​​inserted into the major groove of DNA to recognize the DNA sequence.

 

Zinc finger motif: binding site using zinc as a prosthetic group

It consists of one α-helical structure and two β-fold structures that recognize DNA sequences, and zinc in the middle stabilizes this structure. Zinc binds to 2 histidines in the α helix and 2 cysteines in the β screen through coordination bonds, and the α helix recognizes a wide groove in DNA.

 

Leucine zipper motif: Forms dimers, mainly homodimers but forms heterodimers

Two long α-helices form a dimer with each other, and the leucines arranged in the α-helices are very hydrophobic, so that a strong hydrophobic interaction occurs between the leucines. The unbound α helix has a shape that fits into a wide groove in the DNA like tongs.

 

 

Helix-loop-helix motif: α-helix binds to DNA by forming a dimer similar to a leucine zipper

A short α-helix at the C-terminus and a ring structure bind each other to form a dimer. There are many similarities with the leucine zipper, and the leucine zipper and the protein having a helix-ring-helix motif often have a basic amino acid residue in the α-helix region that recognizes DNA.

 

 

사실 DNA 결합부위는 고등학생 때 일반생물학을 배우면서 그림이 익숙하긴 하지만, 활성화 부위에 대한 언급은 별로 없었던 것으로 기억한다. 활성화 부위를 구성하는 아미노산들이 산성을 많이 띈다는 것 외에 큰 특징은 기억나지 않는다. 산성이 특징이 어떤 중요한 역할을 하는지에 대해서도 두루뭉실하게 넘어간 것 같은데 이를 공부할 기회가 있길 바랍니다.... 너무 시간이 없네요ㅠㅠ 3학년 1학기로 복학했는데 4학년 전공 과목 2개 + 3학년 전공 과목 3개 + 2학년 전공과목 1개 + 교양 1개 듣고 알바까지하려니 너무 바빠요