Every cell of a multicellular organism consists of their complete genome in the nucleus in one or more copies. But, only a unique set of genes are transcribed in a particular cell, defining the individuality of the cell among the other cells in the organism. Many genes are also only transcribed at certain times. The transcription of a gene produces RNA that is translated into a protein. When a particular protein is required for the functioning of the cell, the gene that encodes the protein is transcribed. Thus, that gene is considered as ‘turned on’. When a gene is turned off, the transcription is halted. Several mechanisms are involved in the regulation of gene expression. The regulation of gene expression in eukaryotic cells relies on a group of proteins termed as transcription factors (TFs). In addition to transcription factors, chromatin modifications, RNA splicing, siRNA control mechanisms and cell signaling are also responsible for the regulation of gene expression in eukaryotes.
This article looks at,
What are Transcription Factors
A transcription factor is a protein molecule that controls the activity of a gene by determining whether a particular gene is transcribed into RNA or not. RNA polymerase is the enzyme that catalyzes the synthesis of RNA by using DNA as the template. Transcription factors control the action of RNA polymerase by determining when, where and how efficiently the enzyme functions. Hence, transcription factors may act as either activators that boost gene expression or repressors that decrease the gene expression.
Three types of transcription factors are found: general factors, upstream factors, and inducible factors. General transcription factors are required for the initiation of transcription of coding genes. The initiation complex that is formed by general transcription factors is called the basal transcription apparatus. Upstream transcription factors are involved in the recognition of specific short consensus elements that are located upstream to the transcription start point. Inducible factors function similar to upstream transcription factors, further regulating gene expression by binding to response elements. The function of activator on transcription is shown in figure 1.
Having explained transcription factors, now let us see how do transcription factors bind to DNA.
How Do Transcription Factors Bind to DNA
Transcription factors belong to diverse families of proteins that function as multi-subunit protein complexes. They directly bind to cis-regulatory DNA sequences or motifs that occur upstream to the TATA box of the promoter sequence. These motifs are usually about 6 to 10 base pairs long. Transcription factors also bind either to enhancers or silencers that affect transcription. Enhancers occur nearby the gene – upstream, downstream or within the introns. They turn on the gene expression while silencers turn off the gene expression. Transcription factors change their 3-D structure while accompanying the binding to DNA.
The forming complex of transcription factors and promoter along with the enhancers recruit RNA polymerase II. The influence of the transcription factors can be either positive or negative depending on the overall impact of the entire transcription factor complex. Transcription factors consist of multiple functional domains to bind with sequence motifs as well as the other transcription factors called co-activators, RNA polymerase II, chromatin remodeling complexes and small non-coding RNAs. Two transcription factors bind to two adjacent motifs on the DNA strand and combine to form a dimer, which bend the DNA. This process is considered as a part of the gene activation process. Chromatin structure also allows coactivators to associate together. Some transcription factors act as tethering elements between distinct promoters and enhancers with the aid of other proteins as well. Eukaryotic transcription activator complex is shown in figure 2.
In addition to activation of the gene expression, some transcription factors are involved in the repression of gene expression. Repressors may block general transcription factors that activate the gene expression. Most of the transcription factors are capable of regulating many gene expressions while a few transcription factors are capable of regulating only selected gene expressions. Since transcription factors control the expression of most genes that are involved in the development of an organism, the defective expression of transcription factor genes may cause the irregular development of the organism.
Transcription factors regulate the gene expression in eukaryotes. The initiation of the transcription is governed by transcription factors. These type of transcription factors are called activators. They turn the gene on. Other than activating the transcription, transcription factors can repress the gene expression as well. The genes are turned off by the binding of repressors. Transcription factors bind to the regulatory elements of the promotor region. During gene activation, transcription factors also bind to the enhancer regions, forming a loop that recruits RNA polymerase II in order to initiate the transcription. Repressors block general transcription factors to the regulatory elements of DNA.
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1. “0338 RNA Polymerase Binding” By OpenStax – https://cnx.org/contents/[email protected]:fEI3C8Ot@10/Preface (CC BY 4.0) via Commons Wikimedia
2. “Transcription Factors” By Kelvinsong – Own work (CC BY 3.0) via Commons Wikimedia