![]() Dynamic balance between activation and repression regulates pre-mRNA alternative splicing during heart development. 1998 May;19(5):681-2. The dynamic balance between heart function and immune activation. Bachetti T, Ferrari R. Comment on Eur Heart J. Sequential Activation of Metabolic Pathways: a Dynamic Optimization Approach. Zaslaver et al. Observed well defined temporal patterns in gene expression data. ![]() Official Symbol SIRT1 provided by Official Full Name sirtuin 1 provided by Primary source See related Gene type protein coding RefSeq status REVIEWED Organism Lineage Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo Also known as SIR2; SIR2L1; SIR2alpha Summary This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008] Expression Ubiquitous expression in adrenal (RPKM 17.4), testis (RPKM 16.6) and 25 other tissues Orthologs. These reference sequences exist independently of genome builds. These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in above. Genomic • NG_050664.1 RefSeqGene Range 5008.38729 Download,, mRNA and Protein(s) • → NAD-dependent protein deacetylase sirtuin-1 isoform b Status: REVIEWED Description Transcript Variant: This variant (2) contains an alternate in-frame exon in the 5' coding region and uses a downstream start codon, compared to variant 1. Isoform b has a shorter N-terminus, compared to isoform a. Source sequence(s) Consensus CDS UniProtKB/Swiss-Prot UniProtKB/TrEMBL, Related, Conserved Domains (1) Location: 1 → 194 SIR2; SIR2 superfamily of proteins includes silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation, where the acetyl group from the lysine epsilon-amino group is transferred to the ADP-ribose moiety of NAD+. • → NAD-dependent protein deacetylase sirtuin-1 isoform c Status: REVIEWED Description Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region and uses an alternate translation start site compared to variant 1. The encoded isoform (c) is shorter and has a distinct N-terminus compared to isoform a. Source sequence(s) Consensus CDS UniProtKB/Swiss-Prot UniProtKB/TrEMBL Related,,, Conserved Domains (1) Location: 12 → 186 SIR2; SIR2 superfamily of proteins includes silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation, where the acetyl group from the lysine epsilon-amino group is transferred to the ADP-ribose moiety of NAD+. • → NAD-dependent protein deacetylase sirtuin-1 isoform a Status: REVIEWED Description Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a). Source sequence(s) Consensus CDS UniProtKB/Swiss-Prot UniProtKB/TrEMBL Related,,, Conserved Domains (1) Location: 254 → 489 SIRT1; SIRT1: Eukaryotic group (class1) which includes human sirtuins SIRT1-3 and yeast Hst1-4; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein/histone deacetylation. The following sections contain reference sequences that belong to a specific genome build. This section includes genomic Reference Sequences (RefSeqs) from all assemblies on which this gene is annotated, such as RefSeqs for chromosomes and scaffolds (contigs) from both reference and alternate assemblies. ![]() Model RNAs and proteins are also reported here. Reference GRCh38.p7 Primary Assembly Genomic • NC_000010.11 Reference GRCh38.p7 Primary Assembly Range 6788390 Download,, Alternate CHM1_1.1 Genomic • NC_018921.2 Alternate CHM1_1.1 Range 6990153 Download. The complex process regulating gene expression is often compared to following a recipe. Miss a genetic ingredient, or add it in the wrong order, and you could have a disaster on your hands. New research from the Stowers Institute for Medical Research in Kansas City suggests the process may be more like a battle between two opposing genetic forces rather than a step-wise assembly of ingredients. In their report, published online on November 14, 2016 in Genome Research, Stowers researchers examined regions of fruit fly DNA, called enhancers, which increase the likelihood of gene expression. The open-access article is titled “Drosophila Poised Enhancers Are Generated During Tissue Patterning with the Help of Repression.” Gene expression is the process of turning genes on or off, and is crucial for creating specific cells in the body such as nerve cells or cells that make up skin and bone. But a duel comes first. Stowers Associate Investigator Julia Zeitlinger, Ph.D., and Postdoctoral Research Associate Nina Koenecke, Ph.D., discovered that DNA enhancers engage in an ongoing contest between activation and repression, which results in a different epigenetic state of the histone proteins around which DNA is wrapped. Activation sparks the addition of acetyl groups to histones, which in turn loosen their grip on DNA enhancers, allowing them to be switched on. Repression, on the other hand, removes this acetylation mark and prevents the switch from ever being flipped. 'Through this balance between forces you can shift an enhancer more easily from inactivity to activity,' Dr. Zeitlinger says. Enhancer activation and repression are known to occur both in the fruit fly Drosophila melanogaster and in mammals. But repression is much less studied in mammals. The finding therefore clarifies the often misunderstood role of repression in DNA enhancers, and underscores its importance as an action, and not just an inaction. Typically, activation gets the most credit for its role in gene expression. For example, enhancers that are epigenetically modified but still inactive have been thought to be 'poised' for future action. However, this new evidence suggests that 'poised' enhancers - rather than lacking a key ingredient for activation - may be repressed. 'When there is an opposition between the two enzymes responsible for acetylation state, it creates an ultra-sensitivity under some conditions,' Dr. Zeitlinger says. 'With just a little more activation, this can create a very dramatic switch in the enhancer's activity. This mechanism could allow a gene being turned on in some cells, while turned off in other cells of the body.' In this study, which focused on enhancers of genes important for specifying the fruit fly body plan, Dr. Zeitlinger and her colleagues drew on knowledge from diverse sources - developmental genetics and its mechanistic analyses of DNA enhancers, mechanistic studies on histone modifications, and insights from global genomics analyses using next-generation sequencing - to develop their unifying model of how DNA enhancers work. They used ChIP-seq analysis to generate high-resolution maps of DNA enhancers under different conditions. Zeitlinger's long-term goal is to map and understand DNA enhancers more extensively. There are hundreds of thousands of enhancers in the human genome. Such insight could provide understanding into diseases and developmental disorders caused by DNA enhancer mutations, and give us a glimpse into the genetic forces that have contributed to human evolution. Other Stowers contributors include Jeff Johnston, Qiye He, Ph.D., and Samuel Meier. IMAGE The image indicates how activation and repression signals actively compete to regulate the amount of acetyl groups at histones near enhancers. (Image courtesy of the Zeitlinger Lab).
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