Why is control of gene expression necessary

Eukaryotic DNA is wrapped around protein complexes called histone octamers, which has the effect of packaging the DNA into a compact form such that it fits inside the nucleus. However, this also limits access of regulatory factors to their target sites. As the mechanisms of transcriptional activators are being uncovered, more and more are being found that act by relieving chromatin-induced repression.

Mutations in components of the complex resulted in decreased activity of certain target genes. Biochemical experiments carried out later on showed that this was indeed the case. A second mechanism by which chromatin-induced repression is relieved is by histone acetylation. Histones are positively charged proteins and hence interact tightly with DNA, which is negatively charged.

Acetylation of histones reduces their net positive charge, which loosens their interaction with DNA and increases transcription factor binding. Several transcription factors in a variety of organisms have now been found to be acetyltransferases; in effect, they can acetylate histones. In addition, some transcriptional repressors in yeast and mammals have been found to be histone deacetylases.

In fact, the protein MeCP2, which binds to methylated DNA, has been found to function in a complex with a histone deacetylase. Thus, methylation would lead to binding of this complex, causing deacetylation of histones and a more condensed chromatin structure.

Methylated DNA has long been known to be associated with transcriptionally inactive genes, and inroads into the study of histone acetylation have finally provided an explanation for this. Stryer, Lubert. New York: W. Freeman and Company, Mutations in o yielded cells that constitutively continually expressed the lac operon, whereas mutations in i fell into two categories; one in which the lac operon was constitutively expressed, and the other in which it was uninducible could not be expressed.

Subsequent experiments showed that i was a gene for a diffusible protein that was the repressor of the lac operon, whereas o was a DNA sequence to which a repressor bound.

This was consistent with the mutant results: A mutation in o would disrupt the binding of the repressor protein, leading to constitutive expression of the lac operon, and a mutation in i would either prevent the repressor from binding to o, resulting in constitutive activation, or render the repressor unresponsive to the inducer, lactose, which would cause uninducibility. Because i was diffusible could move within the cell and could interact with any piece of DNA containing its target sequence, it was called a trans-acting factor trans means "across".

In contrast, o only affects the genes to which it is physically linked and so has been called a cis-acting factor cis means "together". They purified the lac repressor, encoded by i, and found that it bound to a 30 base-pair region of DNA spanning the transcription initiation site, consistent with the location of o. In addition, they found that the lac repressor released its hold on o when bound to allolactose, a derivative of lactose. In the laboratory the DNA-binding domain and the transactivation domain—the two functional domains—can be mixed and matched between different transcription factors to yield hybrid molecules that still function, albeit differently from the original proteins.

This feature has been exploited experimentally. For example, the relative strengths of various activation domains can be assessed by fusing each to the same DNA-binding domain and determining the rate at which each promotes transcription.

Mutations in the MeCP2 cause Rett syndrome, an X-linked dominant disorder marked by seizures, abnormal movements, and mutism. Toggle navigation.

Photo by: fusebulb. Control in Prokaryotes Negative Control. Eukaryotic Transcription Regulation of transcription is by necessity far more complex in eukaryotic cells cells with a nucleus than in prokaryotic cells. Structure of Transcriptional Activators Many transcriptional activators are essentially modular in structure in that the DNA-binding domain and the transactivation or activation domain can almost be thought of as two distinct proteins that are physically linked.

Regulation of Transcriptional Activators Regulation of transcription sometimes occurs via the simple presence or absence of transcription factors.

Transcriptional Repression Transcriptional repressors, like activators, bind cis-acting sequences in the genes they regulate and are modular in structure, possessing distinct DNA-binding and repressor domains. The Role of Chromatin Although transcriptional repressors often participate in gene regulation, it must be kept in mind that the very nature of DNA in eukaryotic cells tends to keep genes in the repressed state.

Bibliography Stryer, Lubert. Learn more. The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health. Can genes be turned on and off in cells?

From Genetics Home Reference. For example, the enzyme Dicer finds double-stranded regions of RNA and cuts out short pieces that can serve in a regulatory role. Argonaute is another enzyme that is important in regulation of small noncoding RNA—dependent systems. Here we offfer an introductory article on these RNAs, but more content is needed; please contact the editors if you are interested in contributing.

Imprinting is yet another process involved in eukaryotic gene regulation; this process involves the silencing of one of the two alleles of a gene for a cell's entire life span. Imprinting affects a minority of genes, but several important growth regulators are included. For some genes, the maternal copy is always silenced, while for different genes, the paternal copy is always silenced.

The epigenetic marks placed on these genes during egg or sperm formation are faithfully copied into each subsequent cell, thereby affecting these genes throughout the life of the organism.

Still another mechanism that causes some genes to be silenced for an organism's entire lifetime is X inactivation. In female mammals, for instance, one of the two copies of the X chromosome is shut off and compacted greatly. As the possible role of regulatory noncoding RNAs in this process is investigated, more information regarding X inactivation will no doubt be discovered.

All rights reserved. Hoopes, L. Nature Education 1 1 Atavism: Embryology, Development and Evolution. Gene Interaction and Disease. Genetic Control of Aging and Life Span. Genetic Imprinting and X Inactivation. Genetic Regulation of Cancer. Obesity, Epigenetics, and Gene Regulation. Chromatin Remodeling and DNase 1 Sensitivity.

Chromatin Remodeling in Eukaryotes. The Role of Methylation in Gene Expression. Gene Expression Regulates Cell Differentiation. DNA Transcription. They pursue this interest through the use of molecular biology, molecular genetic, and biochemical approaches involving diverse experimental systems that bear on different aspects of gene regulation.

Much of eukaryotic gene expression is regulated at the transcriptional level, and the lab has made seminal contributions in transcription factor discovery, understanding the role of basic transcription factors in gene regulation, and elucidating transcription activation mechanisms. Recently, the lab has studied transcriptional regulation in cancer development and has made significant contributions to our understanding of oncogene-directed epigenetic silencing.

Mitochondrial and metabolic perturbations result in numerous alterations in gene expression. The Haynes Lab focuses on the mitochondrial UPR, an intra-cellular stress response that modulates gene expression to repair and recover mitochondrial activity. We have uncovered a novel form of transcriptional regulation based on organelle partitioning of a single transcription factor ATFS-1 in worms, ATF5 in mammals that allows cells to evaluate mitochondrial function or dysfunction and adjust transcription accordingly.

Researchers in the laboratory examine how ATFS-1 is further regulated and integrates with other metabolic stress response pathways to promote survival during mitochondrial dysfunction. In their most recent studies, the Kaufman Lab has discovered multiple nucleolar proteins associated with the CAF-1 p subunit. Notably, p depletion causes redistribution of multiple nucleolar proteins and reduces nucleolar association with repetitive element-containing loci.

Furthermore, the nucleolar functions of p are separable from its interactions with the other subunits of the CAF-1 complex. Together, these data define novel functions for a separable domain of the p protein, regulating protein and DNA interactions at the nucleolus.

The Mao laboratory studies transcriptional regulation mediated by several signaling pathways Hedgehog, Wnt and Hippo in tissue stem cells, progenitors, and transformed cancer cells. They use RNAseq, ChIPseq and Bioinformatics to investigate how tissue- or cancer-specific transcriptional output of these pathways is achieved. The Socolovsky lab has identified an epigenetic switch that controls the transition from self-renewal to differentiation in erythroid progenitors.

Interestingly, this cell fate decision is orchestrated by the cell cycle and is associated with an unusual process in which there is global loss of genomicDNA methylation , the first such instance to be identified in somatic cells. The Wolfe Lab focuses on multiple aspects of gene expression, including transcriptional and post-transcriptional control.

They are also interested in developing new tools for targeted gene regulation. In addition, the Wolfe Lab is part of the Innate Immune Gene Regulatory Project , a collaborative effort to understand the regulatory pathways that underpin the response of Dendritic cells to pathogens.

Regarding post-transcriptional control of gene expression, they are focused on understanding the role of miR in pancreatic endocrine cell development using zebrafish as a model. The life and death of cells Modeling cancer Bioinformatics Editing the genome Finding new treatments for cancer What controls gene expression? How do tumors grow and spread? Metabolism and disease Infection and disease.

What controls gene expression? Bach Lab One of the main goals of the research carried out in the Bach lab is to understand mechanisms controlling gene expression during mammalian embryogenesis.