Transcriptional regulation

예전에 공부했던 거긴한데...한번 다시 읽어볼 기회가 생겨 포스팅해보겠습니다.. TATA box에 대해 연구하면서 한번 팠던 내용이긴 합니다... 무려 3년이 넘었네요

 

Let's look at how activators and transcriptional proteins interact to promote transcription.

 

DNA-bound activators interact with the mediator complex near the promoter by twisting and folding the DNA itself. The mediator complex is a large complex that attracts several proteins to the promoter region so that transcription can be initiated or captured through direct interaction with transcription machinery.

 

As shown in the schematic above, the mediator complex directly induces PolII (RNA polymeraseII).
 
However, depending on which activators are involved, it may be promoted slowly or rapidly.

Proteins that play an important role here are the integration host factor (IHF) proteins, which bend and twist DNA, allowing distant amplifier sequences to come close to the promoter. As an example, the cut gene of Drosophila is catalyzed by an amplifier that is about 100,000 bp away.

A protein called Chip is identified as a protein involved in the interaction between the amplifier and the promoter.

As a model for this protein, it is believed that it binds to several DNA binding sites between the amplifier and the promoter, creating several small loops in the DNA that allow the amplifier and the promoter to interact.

 

Another method may be to bend the chromatin itself instead of bending the DNA, but not much is known about this part. However, activators can also promote transcription by changing the structure of chromatin, which unwinds the structure of chromatin by attracting HATs or nucleosome modifying enzymes.

 

흥미로운 부분은 DNA를 구부리는 것이 아니라 염색질을 구부리는 방법에 대한 연구가 부족하다는 점입니다. 활성인자가 염색질의 구조를 변화시켜 전사를 촉진할 수 있다는 점도 고등학생인 그 당시 신기한 내용이였습니다.

The chromatin structure is unraveled or the nucleosome is remodeled to expose promoters or other regulatory regions to promote transcription.

In particular, when an acetyl group is added to histone, several proteins having a bromodomain can be bound. TFIID, one of the universal transcription factors, can better recognize and bind acetylated nucleosomes. In particular, these proteins that control the structure of chromatin become more important during cell division. What happens to DNA during cell division?

It is condensed as much as possible so that it can be seen under a microscope. However, even in this state, certain genes must continue to be expressed. Even if there are no histone-modifying enzymes such as HATs, genes that are easily expressed need the help of enzymes such as HATs during the cleavage phase. That is, the combination of necessary activators or chromatin regulatory proteins may vary depending on the cell cycle or the type of gene.

 

 

There are other ways in which activators promote transcription. Transcription is a much more unstable mechanism than DNA replication. During transcription, RNA polymerase often breaks away from DNA or stops at will. Proteins that reduce this problem and improve progression include elongation factors such as ELL-based elongation factors and proteins such as TFIIS.

These elongation factors can also be induced by the mediator complex. The transcription of the HSP70 gene in Drosophila is promoted by an activator called GAGA-binding factor. However, if there is no protein called HSF, transcription stops and stops near the promoter. HSF is a protein that is activated when there is heat shock. HSF binds an elongation factor called P-TEF to transcription machinery, which phosphorylates the C-terminal tail of RNA polymerase by P-TEF, enabling transcription to continue from the point of cessation.

Promoter 탈출과 유사한 기작인 것 같습니다.

 

Thus, the HSP70 gene is only activated in the presence of heat shock. Similar to this, HIV also stops transcription in the middle when P-TEF does not participate in the transcriptional machinery. HIV uses RNA-binding protein (TAT) that recognizes a sequence near the RNA initiation site. If RNA polymerase ceases to continue transcription and is in a quiescent state, TAT and RNA polymerase can interact, and as a result, P-TEF can participate in the transcriptional machinery.

 

제가 조금 더 파보고 싶었던 부분이긴 한데 heat shock에 따른 활성화 유전자의 염기비율도 흥미로운 연구주제가 될 것 같긴 합니다. TATA box 연구에서 염기비율에 따라 persistence length가 달라지는 것을 확인하였으니 결국 heat shock에 따른 활성화 유전자도 염기비율과 관련이 있지 않을까 생각합니다.