How is gene expression regulated
Gene regulation is the process of turning genes on and off. During early development, cells begin to take on specific functions. Gene regulation ensures that the appropriate genes are expressed at the proper times. Gene regulation can also help an organism respond to its environment. Gene regulation is accomplished by a variety of mechanisms including chemically modifying genes and using regulatory proteins to turn genes on or off. In the human genome, there are a little less than 20, genes.
In some cells, many genes are active--say, 10,and the other 10, would be inactive. Should we cure disease? Do edits we make today have unforeseen impacts to future generations? How does commercialization of gene editing technologies fit in? While this debate continues, leaders in genetics and bioethics have proposed a moratorium on germline gene editing.
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Begin your journey with Learn Genomics. Every cell in the human body contains the beta globin gene and the corresponding upstream regulatory sequences that regulate expression, but no cell type other than red blood cells expresses beta globin. Scientists can use a technique called DNA footprinting to map where transcription factors bind to specific regulatory sequences.
When Reddy et al. See Figure 1. RNA polymerase in prokaryotes can access almost any promoter in a DNA strand without the presence of activators or repressors.
Thus, the "ground state" of DNA expression in prokaryotes is said to be nonrestrictive, or "on. In many eukaryotic organisms, the promoter contains a conserved gene sequence called the TATA box. Various other consensus sequences also exist and are recognized by the different TF families. Transcription is initiated when one TF binds to one of these promoter sequences, initiating a series of interactions between multiple proteins activators, regulators, and repressors at the same site, or other promoter, regulator, and enhancer sequences.
Ultimately, a transcription complex is formed at the promoter that facilitates binding and transcription by RNA polymerase. As in prokaryotes, eukaryotic repressor molecules can sometimes bind to silencer elements in the vicinity of a gene and inhibit the binding, assembly, or activity of the transcription complex, thus turning off expression of a gene. Positive regulation by TFs that are activators is common in eukaryotes.
Considering the restrictive transcriptional ground state, it is logical that positive regulation is the predominant form of control in all systems characterized to date. Many activating TFs are generally bound to DNA until removed by a signal molecule, while others might only bind to DNA once influenced by a signal molecule.
The binding of one type of TF can influence the binding of others, as well. Thus, gene expression in eukaryotes is highly variable , depending on the type of activators involved and what signals are present to control binding.
Even when transcription factors are present in a cell, transcription does not always occur, because often the TFs cannot reach their target sequences. The association of the DNA molecule with proteins is the first step in its silencing.
The associated DNA and histone proteins are collectively called chromatin; the complex is tightly bonded by attraction of the negatively charged DNA to the positively charged histones Table 1. The state of chromatin can limit access of transcription factors and RNA polymerase to DNA promoters, contributing to the restrictive ground state of gene expression.
In order for gene transcription to occur, the chromatin structure must be unwound. Chromatin structure contributes to the varying levels of complexity in gene regulation. It allows simultaneous regulation of functionally or structurally related genes that tend to be present in widely spaced clusters or domains on eukaryotic DNA Sproul et al.
Interactions of chromatin with activators and repressors can result in domains of chromatin that are open, closed, or poised for activation. Chromatin domains have various sizes and different extents of stability. These variations allow for phenomena found solely in eukaryotes, such as transcription at various stages of development and epigenetic memory throughout cell division cycles. They also allow for the maintenance of differentiated cellular states, which is crucial to the survival of multicellular organisms Struhl, As you have seen, the state of chromatin structure at a specific region in eukaryotic DNA, along with the presence of specific transcription factors, works to regulate gene expression in eukaryotes.
However, this complex interplay between proteins that serve as transcriptional activators or repressors and accessibility to the regulatory sequence is still just part of the story.
Epigenetic mechanisms, including DNA methylation and imprinting , noncoding RNA , post-translational modifications, and other mechanisms, further enrich the cellular portfolio of gene expression control activities. Pulverer, B. Sequence-specific DNA-binding transcription factors. Nature Milestones doi: Reddy, P. Genomic footprinting and sequencing of human beta-globin locus: Tissue specificity and cell line artifact.
Journal of Biological Chemistry , — Remenyi, A. Combinatorial control of gene expression. Regulation of transcription in eukaryotes. In The cell: A molecular approach. Sunderland, MA: Sinauer Associates. Kimball, John W. The human and chimpanzee genomes. OpenStax College, Biology. Eukaryotic transcription gene regulation.
Regulation of gene expression. Phillips, T. Regulation of transcription and gene expression in eukaryotes. Nature Education , 1 1 , Purves, W. Transcriptional regulation of gene expression.
In Life: The science of biology 7th ed. Reece, J. Eukaryotic gene expression is regulated at many stages. In Campbell Biology 10th ed. San Francisco, CA: Pearson. To understand how gene expression is regulated, we must first understand how a gene codes for a functional protein in a cell. The process occurs in both prokaryotic and eukaryotic cells, just in slightly different manners. Prokaryotic organisms are single-celled organisms that lack a cell nucleus, and their DNA therefore floats freely in the cell cytoplasm.
To synthesize a protein, the processes of transcription and translation occur almost simultaneously. When the resulting protein is no longer needed, transcription stops. As a result, the primary method to control what type of protein and how much of each protein is expressed in a prokaryotic cell is the regulation of DNA transcription. All of the subsequent steps occur automatically.
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