Talk:Silencer (genetics)

message: An important DNA sequence that is found in both eukaryotes and prokaryotes are silencers. Silencers are capable of binding transcription regulation factors called repressors. When repressors are bound to the silencers, RNA polymerase is prevented from transcribing these specific DNA sequences and will decrease or fully suppress RNA synthesis. If transcription is prevented, proteins cannot be synthesized because there are no mRNA templates to translate the proteins. 
DNA (deoxyribonucleic acid) contains genes which are the hereditary material located in the nuclei of eukaryotic and prokaryotic cells. DNA sequences are made up of four chemical bases: adenine, guanine, cytosine, and thymine. These bases also form base pairs held together by hydrogen bonds along the double helix structure of DNA: adenine and thymine form a base pair and ctyosine and guanine form a base pair. 
These base pairs also create DNA sequences that can be transcribed to form proteins. RNA polymerase, a DNA-dependent enzyme, produces RNA (ribonucleic acid) using DNA sequences as a template. This RNA will then be used for future synthesis of proteins which activates or inactivates gene expression  in cells. RNA is similar to DNA except that instead of the nucleic acid  thymine, RNA contains uracil which forms a base pair with adenine. Once the RNA has been transcribed from the DNA, referred to as messenger RNA or mRNA, it will be used as a template by amino acids to translate proteins.
Sungta (talk) 23:01, 20 March 2013 (UTC)
thread_title:  Summary 

message: Introduction
An important DNA sequence that is found in both eukaryotes and prokaryotes are silencers. Silencers are capable of binding transcription regulation factors called repressors. When repressors are bound to the silencers, RNA polymerase is prevented from transcribing these specific DNA sequences and will decrease or fully suppress RNA synthesis. If transcription is prevented, proteins cannot be synthesized because there are no mRNA templates to translate the proteins. 
DNA (deoxyribonucleic acid) contains genes which are the hereditary material located in the nuclei of eukaryotic and prokaryotic cells. DNA sequences are made up of four chemical bases: adenine, guanine, cytosine, and thymine. These bases also form base pairs held together by hydrogen bonds along the double helix structure of DNA: adenine and thymine form a base pair and ctyosine and guanine form a base pair. 
These base pairs also create DNA sequences that can be transcribed to form proteins. RNA polymerase, a DNA-dependent enzyme, produces RNA (ribonucleic acid) using DNA sequences as a template. This RNA will then be used for future synthesis of proteins which activates or inactivates gene expression  in cells. RNA is similar to DNA except that instead of the nucleic acid  thymine, RNA contains uracil which forms a base pair with adenine. Once the RNA has been transcribed from the DNA, referred to as messenger RNA or mRNA, it will be used as a template by amino acids to translate proteins. Sungta (talk) 23:39, 2 April 2013 (UTC)
thread_title:  First Draft of Article 

message: Mutations lead to not only observable phenotypic influences in an individual but also alterations that are undetectable phenotypically. Silencers, being encoded in the genome, are susceptible to such alterations, which, in many cases, lead to severe phenotypical and functional abnormalities. In general terms, mutations in silencer elements or regions could lead to either the inhibition of the silencer’s action or to the persisting repression of a necessary gene. Thus, leading to the expression or suppression of an undesired phenotype, which then translates into impacts on the normal functionality of certain systems in the organism. Among the many silencer elements and proteins, REST/NSRF is an important silencer factor that has a variety of impacts not only in neural but also in other areas of development. In fact, in many cases, REST/NSRF acts in conjunction with RE-1/NRSE to repress and influence non-neuronal cells.  Its effects range from humans to frogs, Xenopus laevis to be more specific, having innumerous repercussions not only in phenotype but also in development. In humans, a deficiency in the REST/NSRF silencer element has been correlated to Huntington’s disease, due to the decrease in the transcription of BDNF. Furthermore, ongoing studies indicate that NRSE is involved in the regulation of the ANP gene, which when overexpressed can lead to ventricular hypertrophy.  Finally, in Xenopus laevis, REST/NRSF malfunction or damage has been associated to abnormal ectodermal patterning during development and significant consequences in neural tube, cranial ganglia, and eye development. Hence, modification in silencer elements and sequences can result in either devastating changes or unnoticeable ones. 
===REST/NSRF and Huntington’s Disease===
Huntington’s disease (HD) is an inherited neurodegenerative disorder, which has the emergence of its symptoms during an individual’s mid-adulthood. The most noticeable symptoms of this progressive disease are cognitive and motor impairments as well as behavioral alterations.  These impairments can develop into dementia, chorea, and eventually death. In the molecular level, HD results from a mutation in the huntingtin protein (Htt). More specifically, there is an abnormal repetition of a CAG sequence towards the 5’-end of the gene, which then leads to the development of a toxic polyglutamine (polyQ) stretch in the protein. The mutated Htt protein affects an individual’s proper neural functions by inhibiting the action of REST/NRSF.
REST/NRSF is an important silencer element that binds to regulatory regions to control the expression of certain proteins involved in neural functions. The mechanistic actions of huntingtin are still not fully understood, but a correlation between Htt and REST/NRSF exists in HD development. By attaching to the REST/NRSF, the mutated huntingtin protein inhibits the action of the silencer element, and retains it in the cytosol. Thus, REST/NRSF cannot enter the nucleus and bind to the 21 base-pair RE-1/NRSE regulatory element. An adequate repression of specific target genes are of fundamental importance, since many are involved in the proper development of neuronal receptors, neurotransmitters, synaptic vesicle proteins, and channel proteins. A deficiency in the proper development of these proteins can cause the neural dysfunctions seen in Huntington’s disease. In addition to the lack of repression due to the inactive REST/NRSF, mutated huntingtin protein can also decrease the transcription of the brain-derived neurotropic factor (BDNF) gene. BDNF influences the survival and development of neurons in the central nervous system as well as the peripheral nervous system. This abnormal repression occurs when the RE1/NRSE region within the BDNF promoter region is activated by the binding of REST/NRSF, which leads to the lack of transcription of the BDNF gene.  Hence, the anomalous repression of the BDNF protein suggests a significant impact in Huntington’s disease. 
===REST/NRSF and Ventricular Hypertrophy in Mammals===
REST/NRSF in conjunction with RE1/NRSE also acts outside the nervous system by acting as regulators and repressors.  Researches have linked RE1/NRSE activity with the regulation of expression of the atrial natriuretic peptide (ANP) gene. A NRSE regulatory region is present in the 3’untranslated region of the ANP gene, and acts as a mediator for the appropriate expression of the gene. The protein encoded by the ANP gene is important during embryonic development for the maturation and development of cardiac myocytes.  However, during early childhood and throughout adulthood, ANP expression is suppressed or kept to a minimum in the ventricle. Thus, an abnormal induction of the ANP gene can lead to ventricular hypertrophy, and severe cardiac consequences.  In order to maintain the gene repressed, NRSF (neuron-restrictive silencer factor) or REST binds to the NRSE region in the 3’untranslated region of the ANP gene. Furthemore, the NRSF-NRSE complex recruits a transcriptional corepressor known as mSin3. Thus, leading to the activity of histone deacetylase in region, and the repression of gene expression. Therefore, studies have revealed the correlation between REST/NRSF and RE1/NRSE in regulating the ANP gene expression in ventricular myocytes. A mutation in either the NRSF or NRSE can lead to an undesirable development of ventricular myocytes, due to lack of repression, which can then cause ventricular hypertrophy. Left ventricular hypertrophy, for example, increases an individual’s chance of sudden death due to a ventricular arrhythmia resulting from the increased ventricular mass (8).   In addition to the influence on the ANP gene, the NRSE sequence regulates other cardiac embryonic genes, such as BNP, skeletal α-actin, and Na, K – ATPase α3 subunit. Hence, the regulatory activity of both NRSE and NRSF in mammals prevents not only neural dysfunctions, but also physiological and phenotypical abnormalities in other non-neuronal regions  of the body. 
===REST/NRSF in Xenopus laevis===
[The effects and influences of RE1/NRSE and REST/NRSF are significant in non-neuronal cells that require the repression or silencing of neuronal genes. These silencer elements also regulate the expression of genes that do not induce neuron-specific proteins, and studies have shown the extensive impact these factors have in cellular processes. In Xenopus laevis, RE1/NRSE and REST/NRSF dysfunction or mutation demonstrated significant impact on neural tube, cranial ganglia, and eye development.  All of these alterations can be traced to an improper patterning of the ectoderm during Xenopus development. Thus, a mutation or alteration in either the silencing region Re1/NRSE or silencer REST/NRSF factor can disrupt the proper differentiation and specification of the neuroepithelial domain, and also hinder the formation of skin or ectoderm. Furthermore, the lack of these factors result in a decreased production of bone morphogenetic protein (BMP), which translates into a deficient development of the neural crest. Hence, the effects of NRSE and NRSF are of fundamental importance for neurogenesis of the developing embryo, and also in the early stages of ectodermal patterning. Ultimately, inadequate functioning of these factors can result in aberrant neural tube, cranial ganglia, and eye development in Xenopus. Richjoo (talk) 00:28, 3 April 2013 (UTC)
thread_title: Mutated silencers, hereditary diseases, and their effects

message: [The effects and influences of RE1/NRSE and REST/NRSF are significant in non-neuronal cells that require the repression or silencing of neuronal genes. These silencer elements also regulate the expression of genes that do not induce neuron-specific proteins, and studies have shown the extensive impact these factors have in cellular processes. In Xenopus laevis, RE1/NRSE and REST/NRSF dysfunction or mutation demonstrated significant impact on neural tube, cranial ganglia, and eye development.  All of these alterations can be traced to an improper patterning of the ectoderm during Xenopus development. Thus, a mutation or alteration in either the silencing region Re1/NRSE or silencer REST/NRSF factor can disrupt the proper differentiation and specification of the neuroepithelial domain, and also hinder the formation of skin or ectoderm. Furthermore, the lack of these factors result in a decreased production of bone morphogenetic protein (BMP), which translates into a deficient development of the neural crest. Hence, the effects of NRSE and NRSF are of fundamental importance for neurogenesis of the developing embryo, and also in the early stages of ectodermal patterning. Ultimately, inadequate functioning of these factors can result in aberrant neural tube, cranial ganglia, and eye development in Xenopus. Richjoo (talk) 00:28, 3 April 2013 (UTC)
thread_title: REST/NRSF in ''Xenopus laevis''

message: My portion of the article covered the Mechanisms of Silencers. My recent edits to this portion was the inclusion of a figure, and a section on the similarities of enhancers to Silencers. I added to the mechanisms suptopic the example of REST/NRSF. I then added wikilinks throughout my section of the article. Finally, I cleaned up the citations by adding ref names and also added more citations throughout the writing instead of at the end of each paragraphClucaj (talk) 01:46, 7 April 2013 (UTC)
thread_title: Recent Edits

message: Your page looks really great so far.  I read through your page and added some commas and rephrased a few choppy sentences.  I also added some wikilinks including links to dementia and chorea.  You guys have a lot of information and provide some great detail and examples.  Overall I don't think you need to add any new info, or take any out.  You guys have some great pictures and diagrams, but if you can find more I would say to add them to the REST/NRSF sections.  Great Job! Kmcging (talk) 19:28, 11 April 2013 (UTC)
thread_title: Classmate Edit

message: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281776/
http://bejerano.stanford.edu/readings/public/10_Intro_TxRegReview.pdf
http://www.uic.edu/classes/bios/bios100/lecturesf04am/lect15.htm
http://www.ncbi.nlm.nih.gov/books/NBK21572/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1219314/pdf/9512455.pdf
http://www.ncbi.nlm.nih.gov/books/NBK7588/	
http://www.ncbi.nlm.nih.gov/books/NBK10023/
http://www.news-medical.net/health/What-is-DNA.aspx
http://www.ncbi.nlm.nih.gov/pubmed/11238943?dopt=Abstract&holding=npg
http://www.ncbi.nlm.nih.gov/pubmed/7871435
Richjoo (talk) 20:06, 22 March 2013 (UTC)
thread_title:  References 

message: To you awesome BC students: thank you for building up this article!  An interesting section often seen in high-quality molecular biology Wikipedia articles is a 'History and discovery' section, which discusses things like the researcher(s) that discovered the subject, and what led them to that discovery.  Examples include RNA_interference#History_and_discovery, DNA#History_of_DNA_research and Major_urinary_proteins#Discovery, Homologous_recombination#History_and_discovery and DNA_polymerase#History.  This helps give context to the subject.  Would it be feasible to add such a section to this article? Emw (talk) 12:51, 27 April 2013 (UTC)
thread_title:  History and discovery?