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  • Lifelong learning is made possible by recycling of histones, study says | Newswire
    to DNA s thread giving the genetic code support structure and protection Five major types of histone including one called H3 are known and researchers have become interested in the function of variants of these histones which are often very similar to their standard counterparts This new research focused on one such variant H3 3 which closely resembles its main H3 counterpart In a series of experiments using a wide variety of techniques first author Ian Maze a former postdoc in Allis s lab and now an assistant professor at Icahn School of Medicine at Mount Sinai and his colleagues linked plasticity and as a result learning with the destruction and replacement of H3 3 within the neurons of the hippocampus a region of the brain associated with memory among other things They began by looking at histones within the brains of mice and postmortem samples from humans In both cases they found levels of H3 3 increasing with age and finally coming to dominate By feeding the animals food containing a chemical label and following the decay of a radioactive signal naturally found in the human brain samples the researchers determined that rather than remaining in place on DNA throughout life H3 3 is constantly recycled with new H3 3 proteins replacing old ones a process that slows down with age Next they wanted to know what these changes meant In cell culture they linked H3 3 turnover with increased neural activity and then in mice they found that a mentally stimulating environment for mice this means a running wheel toys and plenty of space among other things produced increased turnover of H3 3 in the hippocampus These results suggested a link between H3 3 recycling and neuronal plasticity When the researchers looked to gene expression they found that following stimulation of a neuron the expression of certain genes increased The same genes turned out to be necessary for forming synapses and they were accompanied by significant amounts of H3 3 Their results so far led them to suspect a connection between H3 3 recycling and learning by way of synapse formation They then tested this hypothesis When we put an end to histone turnover in adult mice we found it disrupted normal gene expression patterns associated with plasticity and as a result impaired the animals ability to learn new things For instance they had difficulty distinguishing objects they had previously encountered from new ones Maze says Because some psychiatric diseases such as schizophrenia are associated with deficits in synapses it would be interesting to investigate whether or not histone turnover is involved In additional experiments the researchers reduced histone turnover in embryonic stem cells which have the potential to become any type of cell in an organism with little effect However reducing turnover did alter gene expression in glial cells other brain cells involved in supporting neurons However turnover affected a different set of genes for glial cells and astrocytes than in the neurons It appears the turnover

    Original URL path: http://newswire.rockefeller.edu/2015/07/01/lifelong-learning-is-made-possible-by-recycling-of-histones-study-says/ (2016-02-13)
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  • C. David Allis | Newswire
    of the human body s normal antiviral response in order to slip by it undetected The results have major implications for our understanding of the biology of the seasonal influenza virus and suggest a possible target for a new class of antiviral and anti inflammatory drugs More Tags Alexander Tarakhovsky C David Allis epigenetics histone code histones mimicry Robert G Roeder December 22 2010 Science News Scientists identify protein that drives survival of gastrointestinal tumors Since the introduction of Gleevec as a treatment for gastrointestinal stromal tumors survival rates have climbed dramatically and recurrence has fallen by two thirds But over time many patients develop resistance to the drug Now scientists at Rockefeller University and Memorial Sloan Kettering Cancer Center have identified a molecule that acts as a survival factor for gastrointestinal tumors a finding that may lead to next generation therapies that can pick up where Gleevec leaves off More Tags C David Allis ETV1 GIST Laboratory of Chromatin Biology and Epigenetics Ping Chi August 15 2010 Science News Experiments decipher key piece of the histone code in cell division The division of one cell into two is one of the most basic processes of life One of the many tricks involved is the segregation of copied chromosomes to opposite ends of the cell before it divides New research details for the first time the role of an epigenetic modification to the proteins that package DNA in the fundamental biological phenomenon known as mitosis More Tags C David Allis epigenetics Hironori Funabiki Laboratory of Chromosome and Cell Biology March 10 2010 Science News Scientists track variant of gene regulating protein in embryonic stem cells The path to fully developed cells from embryonic stem cells requires that the right genes are turned on and off at the right times New research from Rockefeller University shows that tiny variations between gene regulating histone proteins play an important role in determining how and when genes are read The finding shows that each region of the genome may be even more specialized than previously expected and may open a new avenue of investigation regarding the mysterious causes of the human genetic disease known as ATR X syndrome More Tags ATR X syndrome C David Allis HIRA Laboratory of Chromatin Biology and Epigenetics January 8 2010 Science News Loss of epigenetic regulators causes mental retardation New findings published in recent issues of Neuron and Science indicate that malfunction of a protein complex that normally suppresses gene activation causes mental retardation in mice and humans and may even play a role in promoting susceptibility to drug addiction More Tags Alexander Tarakhovsky C David Allis Laboratory of Molecular and Cellular Neuroscience Nathaniel Heintz Paul Greengard June 1 2009 Science News Misreading of histone code linked to human cancer The development of blood from stem cell to fully formed blood cell follows a genetically determined program When it doesn t work properly genetic mutations can cause the developing cells to turn cancerous In research published in the

    Original URL path: http://newswire.rockefeller.edu/tag/c-david-allis/ (2016-02-13)
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  • H3.3 | Newswire
    Biology and Epigenetics neuronal plasticity May 4 2015 Science News Odd histone helps suppress jumping genes in stem cells study says The histone variant H3 3 appears to help keep certain genetic elements called retrotransponsons in place in the genome preventing potentially harmful mutations in mouse embryonic stem cells researchers have found This discovery reveals a basic mechanism for epigenetics or the control of inherited traits through means other than

    Original URL path: http://newswire.rockefeller.edu/tag/h3-3/ (2016-02-13)
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  • hippocampus | Newswire
    Tags C David Allis epigenetics H3 3 hippocampus histones Ian Maze Laboratory of Chromatin Biology and Epigenetics neuronal plasticity September 2 2014 Science News Research hints at why stress is more devastating for some Some bounce back from stress while others struggle with it even developing anxiety and depression as a result In experiments with mice researchers have revealed the molecular origins of this so called stress gap More Tags

    Original URL path: http://newswire.rockefeller.edu/tag/hippocampus/ (2016-02-13)
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  • Ian Maze | Newswire
    new connections with one another the basis for learning Their discovery focuses on one particular type of DNA supporting protein the histone H3 3 and its role regulating gene expression More Tags C David Allis epigenetics H3 3 hippocampus histones Ian Maze Laboratory of Chromatin Biology and Epigenetics neuronal plasticity Search for Categories Science News Awards and Honors Campus News Grants Gifts Topics Video Archive 2015 2014 2013 2012 2011

    Original URL path: http://newswire.rockefeller.edu/tag/ian-maze/ (2016-02-13)
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  • Laboratory of Chromatin Biology and Epigenetics | Newswire
    in the genome preventing potentially harmful mutations in mouse embryonic stem cells researchers have found This discovery reveals a basic mechanism for epigenetics or the control of inherited traits through means other than DNA More Tags C David Allis genome H3 3 histones jumping genes Laboratory of Chromatin Biology and Epigenetics Laura Banaszynski retrotransposons Simon Elsässer stem cells November 10 2014 Awards and Honors C David Allis wins the 2015 Breakthrough Prize in Life Sciences Allis is recognized for his foundational research on the unexpected regulation of gene activation by modifications to proteins that package DNA work with implications for many diseases including cancer The Breakthrough Prize is worth 3 million making it the richest prize in the life sciences roughly double the Nobel Prize More Tags Breakthrough Prize C David Allis chromatin epigenetics gene regulation histones Laboratory of Chromatin Biology and Epigenetics December 22 2010 Science News Scientists identify protein that drives survival of gastrointestinal tumors Since the introduction of Gleevec as a treatment for gastrointestinal stromal tumors survival rates have climbed dramatically and recurrence has fallen by two thirds But over time many patients develop resistance to the drug Now scientists at Rockefeller University and Memorial Sloan Kettering Cancer Center have identified a molecule that acts as a survival factor for gastrointestinal tumors a finding that may lead to next generation therapies that can pick up where Gleevec leaves off More Tags C David Allis ETV1 GIST Laboratory of Chromatin Biology and Epigenetics Ping Chi March 10 2010 Science News Scientists track variant of gene regulating protein in embryonic stem cells The path to fully developed cells from embryonic stem cells requires that the right genes are turned on and off at the right times New research from Rockefeller University shows that tiny variations between gene regulating histone

    Original URL path: http://newswire.rockefeller.edu/tag/laboratory-of-chromatin-biology-and-epigenetics/ (2016-02-13)
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  • Discovery links shift in metabolism to stem cell renewal | Newswire
    DNA histone protein complexes called chromatin use the products of cellular metabolism to do so But how specific alterations in metabolic pathways can impact gene expression programs during development and differentiation has remained a mystery says lead researcher C David Allis Joy and Jack Fishman Professor and head of the Laboratory of Chromatin Biology and Epigenetics This collaborative effort with Craig Thompson s lab at Memorial Sloan Kettering reveals that the nutrients a stem cell uses and how it uses them can contribute to a cell s fate by changing the chromatin landscape and as a result influencing gene expression These changes are epigenetic meaning they do not affect genes themselves instead they alter how DNA is packaged making it more or less accessible for expression In this case researchers were interested in a specific type of epigenetic change chemical groups known as methyl groups that attach to chromatin Generally the addition of these methyl groups compacts and silences regions of the genome To maintain their ability to give rise to any type of cell in the body stem cells need all of their genome available and so they must keep methylation in check Some epigenetic marks such as methyl groups are themselves products of metabolism metabolites What s more some other metabolites participate in the reactions that remove methylations making genes available for expression After joining the Allis Lab postdoc Bryce Carey presented an idea that tied these concepts together What if in stem cells the changes to chromatin reflect a unique metabolism that helps to drive reactions that help to keep chromatin accessible This connection would explain how embryonic stem cells are so uniquely poised to activate so much of their genomes Carey says Mouse embryonic stem cells grown in a medium known as 2i are much better at renewing themselves than those grown in the traditional medium containing bovine serum although researchers don t fully understand why Carey and co first author Lydia Finley a postdoc in Thompson s metabolism focused lab compared the metabolism of cells grown in both media Carey and Finley first noticed that the 2i cells did not require glutamine an amino acid most cells need to make the metabolite alpha ketoglutarate an important player in a series of metabolic reactions known as the citric acid cycle and a metabolite that had also been previously implicated in regulation of methylations on chromatin Even without glutamine however the 2i cells managed to produce significant amounts of alpha ketoglutarate To their surprise 2i cells had rewired their metabolism to reduce the breakdown of alpha ketoglutarate in the citric acid cycle where an enzyme normally converts alpha ketoglutarate to succinate to fuel cell growth This resulted in increased alpha ketoglutarate to fuel the reactions that erase methyl groups from chromatin Basic chemistry dictates that you can drive a reaction forward by supplying more of the starting material while taking away the product Since the conversion of alpha ketoglutarate to succinate is linked to the removal of

    Original URL path: http://newswire.rockefeller.edu/2014/12/10/discovery-links-shift-in-metabolism-to-stem-cell-renewal/ (2016-02-13)
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  • alpha-ketoglutarate | Newswire
    to pick a fate or renew themselves In experiments exposure to a key metabolite called alpha ketoglutarate enhanced the renewal of mouse embryonic stem cells More Tags alpha ketoglutarate Bryce Carey chromatin Craig Thompson David Allis differentiation epigenetics Lydia Finley Memorial Sloan Kettering Cancer Center metabolism methylation stem cells Search for Categories Science News Awards and Honors Campus News Grants Gifts Topics Video Archive 2015 2014 2013 2012 2011 more

    Original URL path: http://newswire.rockefeller.edu/tag/alpha-ketoglutarate/ (2016-02-13)
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