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50 Years of the Lyon Hypothesis and X inactivation at the European Cytogeneticists Association ECA conference Porto

50 Years of the Lyon Hypothesis and X inactivation at the European Cytogeneticists Association ECA conference Porto | molcyt | Scoop.it
Mary Lyon’s hypothesis of random inactivation of one X chromosome, leading to sectorial or clonal patterns of gene expression in adult animals, was published in Nature on 22nd May, 1961. Neil Brockdorff from the Department of Biochemistry, Oxford, presented a Plenary talk on the history of X inactivation, including the antecedent work to Lyon’s seminal paper, leading up to his current work dissecting the molecular mechanisms. Despite the comments “50 years and we still don't know how it works” and “we have another 50 years of research in front of us”, the audience was left with the view that progress has been rapid, particularly with the new understanding of involvement of RNA in the processes of silencing.

Even for its time, Lyon's paper was an unusual piece of work: it is less than a page long, and there is not a single experiment reported. It is an ‘ideas’ paper which allows explanation of the results of others. In particular, her work build on publications by Barr and Bertram (1953) with the Barr Body, then the demonstration that XO mice are female, normal and fertile by Welshons and Russell (1959) and Ohno and Hauschka (1960) who showed the Barr body was the sex chromosome. In his talk, Neil too the audience through the development of understanding of the Lyon hypothesis in the subsequent five decades. Interestingly, this approach highlighted the nature of some of the really large areas of exciting scientific developments in each decade, whether the genetics of the 1960s or DNA sequencing of the 1990s.

In the years following publication of the Lyon hypothesis inactivation of one of the copies of the X chromosome in early embryogenesis of female mammals was given experimental proof, notably in cell transplanation experiments by Gardner and Lyon in 1971. Russell came up with the idea of X inactivation centre (Xic) in 1963, based on her studies of mouse strains with balanced X-autosome translocations and silencing of the albino locus. Since only one translocation products was inactivated at a time, she concluded that a bidirectional signal spread and silenced the chromosome. Also in the 1960s, Cattanach genetically mapped the X controlling element, Xce, synonymous with the Xic. In the 1970s advances in cytogenetic methods to detect the inactive X in mouse cells, Giemsa-Kanda staining, the late replication assay, together with identification of variant isozymes for X encoded proteins in different mouse strains drove advances in defining the embryology and phylogeny of X inactivation. Takagi showed that the paternal X is preferentially inactivated in the mouse extra-embryonic tissues, while in maruspials, the congress opening speaker Jenny Marshall Graves showed that it is always the paternal X that is inactivated. Studies from Monk and McClaren, Gartler and others demonstrated reactivation of the inactive X in maturing female primordial germ cells and in cell fusions between pluripotent EC cells and female somatic cells. Although epigenetics was not coined as a phrase, it is clear that reprogramming of inactive X was good indicator for reprogramming of the genome as a whole. Studies in this era also more precisely defined the timing of random X inactivation in female embryos.

The 1980s brought molecular biology to the fore, with studies of DNA methylation as a mechanism for heritable, long-term gene silencing on the inactive X chromosome. Sohaila Rastan, Lyon's only PhD student, refined the location of the X inactivation centre Xic in mouse (1985) and developed model systems for inactivation in mouse. In the 1990s, Brown and Willard (1991) were able to map the Xic in human, and the unexpected Xist gene and associated transcript was found. This gene, expressed only from the inactive X chromosome, produces a long non-coding RNA, localized in the nucleus, but with no protein coding regions nor association with polysomes. By the mid-1990s, experiments proved Xist is necessary and sufficient for X-inactivation.

At this stage, there were two big questions: how is Xist regulated to achieve appropriate patterns of X chromosome activity in female and male embryos? And how does Xist RNA bind in cis and bring about chromosome-wide gene silencing? Neil presented evidence from his own work and that of other labs building towards understanding the molecular basis for the heterochromatic state of the inactive X. Multiple layers of chromatin modification all contribute to the inactive state, and confer stable, heritable, silencing. However, the mechanism(s) for establishment of the inactive X is still not clear: the analysis of the temporal order of inactivation suggests two distinct stages. A mechanistic link to Xist RNA is a work in progress. A clear link of RNA to chromatin inactivation awaits identification of factors with bona-fide RNA-binding domains. As with the earliest work following Mary Lyon’s publication, X-autosome translocations are showing important features including spreading along a gradient of X -inactivation into autosomal regions, evidence that Lyon used in her LINE1 hypothesis of 1999 based on the enrichment of these retrotransposable elements on the X chromosome compared to autosomes. Although Xist RNA is not seen to bind to LINE DNA, Neil’s work has shown that the most highly repressed genes were in L1 LINE rich areas.

In concluding, Neil presented a preliminary and still speculative model of the role for L1 and gene domains in defining giant loop organization on the X chromosome, with clustering of L1s together, and the involvement of RNA, giving small chromatin loops pulling genes into silenced domains. Will another 50 years of work be needed to finalize the mechanisms of X-inactivation?

This article will appear in the Conference summary in the the ECA Newsletter 28 - http://www.e-c-a.eu/EN/content.asp?PID={FFB5E4A1-BDE4-4F11-AF9A-8F06A9C5C516}
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Molecular cytogenetics, genome evolution, biodiversity, botany and plant breeding
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PLoS Pathogens: The Arbuscular Mycorrhizal Symbiosis: Origin and Evolution of a Beneficial Plant Infection

PLoS Pathogens: The Arbuscular Mycorrhizal Symbiosis: Origin and Evolution of a Beneficial Plant Infection | molcyt | Scoop.it

Nicolas Corradi and Paola Bonfante from Canada and Italy review an ancient and ecologically critical fungal lineage: Arbuscular mycorrhizal fungi (AMF) represent a monophyletic fungal lineage (Glomeromycota) that benefits terrestrial ecosystems worldwide by establishing an intimate association with the roots of most land plants: the mycorrhizal symbiosis. This relationship results in an improved acquisition of nutrients (e.g., phosphate and nitrates) from the soil by the plant partners and, in exchange, allows the AMF to obtain the photosynthetically fixed carbon sources (e.g., sugars) necessary for their survival and propagation [1], [2] (Figure 1). This fungal lineage is known to impact the function and biodiversity of entire ecosystems by producing extensive underground networks, composed of hyphae and spores, that interconnect a number of unrelated individual plant species [1], [2]. These networks also function as a significant sink for atmospheric carbon dioxide, and represent significant underground “nutrient highways” that benefit entire plant and microbial communities. Indeed, AMF spores and hyphae are also a valuable source of food for many soil microorganisms (i.e., bacteria, other fungi, and nematodes), and because of their many beneficial effects on terrestrial ecosystems, AMF are widely used in organic agriculture and plant nurseries to improve the growth of economically important species.


Via Kamoun Lab @ TSL
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Affable Nerds and Second Bananas: What Science Communicators Can Learn From Top Gear

Affable Nerds and Second Bananas: What Science Communicators Can Learn From Top Gear | molcyt | Scoop.it

"Why has academia largely ignored one of the world's most popular technology programmes - and what does the show tell us about the effective communication of complex ideas?"

 

A review of a scholarly paper on what we as scientists can learn from Top Gear about presentation of technical material ...

 

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Turbocharge your writing today : Nature : Nature Publishing Group

Turbocharge your writing today : Nature : Nature Publishing Group | molcyt | Scoop.it
Before you can tackle the overwhelming task of huge writing projects, you first need to start writing ... Nature's advice via Trends Plant Sci Twitter
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50 Years of the Lyon Hypothesis and X inactivation at the European Cytogeneticists Association ECA conference Porto

50 Years of the Lyon Hypothesis and X inactivation at the European Cytogeneticists Association ECA conference Porto | molcyt | Scoop.it
Mary Lyon’s hypothesis of random inactivation of one X chromosome, leading to sectorial or clonal patterns of gene expression in adult animals, was published in Nature on 22nd May, 1961. Neil Brockdorff from the Department of Biochemistry, Oxford, presented a Plenary talk on the history of X inactivation, including the antecedent work to Lyon’s seminal paper, leading up to his current work dissecting the molecular mechanisms. Despite the comments “50 years and we still don't know how it works” and “we have another 50 years of research in front of us”, the audience was left with the view that progress has been rapid, particularly with the new understanding of involvement of RNA in the processes of silencing.

Even for its time, Lyon's paper was an unusual piece of work: it is less than a page long, and there is not a single experiment reported. It is an ‘ideas’ paper which allows explanation of the results of others. In particular, her work build on publications by Barr and Bertram (1953) with the Barr Body, then the demonstration that XO mice are female, normal and fertile by Welshons and Russell (1959) and Ohno and Hauschka (1960) who showed the Barr body was the sex chromosome. In his talk, Neil too the audience through the development of understanding of the Lyon hypothesis in the subsequent five decades. Interestingly, this approach highlighted the nature of some of the really large areas of exciting scientific developments in each decade, whether the genetics of the 1960s or DNA sequencing of the 1990s.

In the years following publication of the Lyon hypothesis inactivation of one of the copies of the X chromosome in early embryogenesis of female mammals was given experimental proof, notably in cell transplanation experiments by Gardner and Lyon in 1971. Russell came up with the idea of X inactivation centre (Xic) in 1963, based on her studies of mouse strains with balanced X-autosome translocations and silencing of the albino locus. Since only one translocation products was inactivated at a time, she concluded that a bidirectional signal spread and silenced the chromosome. Also in the 1960s, Cattanach genetically mapped the X controlling element, Xce, synonymous with the Xic. In the 1970s advances in cytogenetic methods to detect the inactive X in mouse cells, Giemsa-Kanda staining, the late replication assay, together with identification of variant isozymes for X encoded proteins in different mouse strains drove advances in defining the embryology and phylogeny of X inactivation. Takagi showed that the paternal X is preferentially inactivated in the mouse extra-embryonic tissues, while in maruspials, the congress opening speaker Jenny Marshall Graves showed that it is always the paternal X that is inactivated. Studies from Monk and McClaren, Gartler and others demonstrated reactivation of the inactive X in maturing female primordial germ cells and in cell fusions between pluripotent EC cells and female somatic cells. Although epigenetics was not coined as a phrase, it is clear that reprogramming of inactive X was good indicator for reprogramming of the genome as a whole. Studies in this era also more precisely defined the timing of random X inactivation in female embryos.

The 1980s brought molecular biology to the fore, with studies of DNA methylation as a mechanism for heritable, long-term gene silencing on the inactive X chromosome. Sohaila Rastan, Lyon's only PhD student, refined the location of the X inactivation centre Xic in mouse (1985) and developed model systems for inactivation in mouse. In the 1990s, Brown and Willard (1991) were able to map the Xic in human, and the unexpected Xist gene and associated transcript was found. This gene, expressed only from the inactive X chromosome, produces a long non-coding RNA, localized in the nucleus, but with no protein coding regions nor association with polysomes. By the mid-1990s, experiments proved Xist is necessary and sufficient for X-inactivation.

At this stage, there were two big questions: how is Xist regulated to achieve appropriate patterns of X chromosome activity in female and male embryos? And how does Xist RNA bind in cis and bring about chromosome-wide gene silencing? Neil presented evidence from his own work and that of other labs building towards understanding the molecular basis for the heterochromatic state of the inactive X. Multiple layers of chromatin modification all contribute to the inactive state, and confer stable, heritable, silencing. However, the mechanism(s) for establishment of the inactive X is still not clear: the analysis of the temporal order of inactivation suggests two distinct stages. A mechanistic link to Xist RNA is a work in progress. A clear link of RNA to chromatin inactivation awaits identification of factors with bona-fide RNA-binding domains. As with the earliest work following Mary Lyon’s publication, X-autosome translocations are showing important features including spreading along a gradient of X -inactivation into autosomal regions, evidence that Lyon used in her LINE1 hypothesis of 1999 based on the enrichment of these retrotransposable elements on the X chromosome compared to autosomes. Although Xist RNA is not seen to bind to LINE DNA, Neil’s work has shown that the most highly repressed genes were in L1 LINE rich areas.

In concluding, Neil presented a preliminary and still speculative model of the role for L1 and gene domains in defining giant loop organization on the X chromosome, with clustering of L1s together, and the involvement of RNA, giving small chromatin loops pulling genes into silenced domains. Will another 50 years of work be needed to finalize the mechanisms of X-inactivation?

This article will appear in the Conference summary in the the ECA Newsletter 28 - http://www.e-c-a.eu/EN/content.asp?PID={FFB5E4A1-BDE4-4F11-AF9A-8F06A9C5C516}
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What is Biodiversity

What is Biodiversity | molcyt | Scoop.it
Biodiversity is a valuable genetic resource and includes all life forms from the unicellular fungi, bacteria to complex multicellular organisms such as plants and mammals.
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FAO Council Adopts Second Global Plan of Action for PGRFA ...

FAO Council Adopts Second Global Plan of Action for PGRFA ... | molcyt | Scoop.it
... and develop strategies to protect, collect and conserve crop wild relatives and wild food plants that are under threat, support use of a wider range of traits for plant breeding, and strengthen seed systems especially of locally ...
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Mendel’s peas – when life was easy | NutsaboutPlants

Mendel’s peas – when life was easy | NutsaboutPlants | molcyt | Scoop.it
At school pupils count and segregate colour and shape according to Mendel. All adds up – such is life at this point, simplified, easy. Not to forget about the biological facts set down in laws that can be memorized and that’s it. While many see in Mendel the father of modern genetics, an example scientist (for both biased and unbiased) research, I personally associate with him first of all the revelation that biology is not as easy as they try to tell you. But, to quote one of my favourite science writers ‘I think you’ll find it’s a bit more complicated than that’. Experimenting and learning about biology means predominantly that things don’t add up, they don’t work, or at least not the way imagined.
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Biodiversity for a world without hunger

Biodiversity for a world without hunger | molcyt | Scoop.it
Biodiversity for food and agriculture is among the earth’s most important resources. Crops, farm animals, aquatic organisms, forest trees, micro-organisms and invertebrates - thousands of species and their genetic variability make up the web of biodiversity in ecosystems that the world’s food and agriculture production depends on.
This biodiversity is indispensable, be it insects pollinating plants, microscopic bacteria needed for making cheese, diverse breeds of livestock needed for making a living even in the harshest of environments, or the thousands of varieties of crops sustaining food security worldwide. For thousands of years, humankind has used, developed and relied on biodiversity for food and agriculture.
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Genetics: Scientists seek diversity in genome study subjects

Genetics: Scientists seek diversity in genome study subjects | molcyt | Scoop.it
Theodosius Dobzhansky wrote in 1973 that "Nothing makes sense in biology except in the light of evolution". Sadly, the essential need for comparative analysis is misunderstood in many areas of biology and genetics. This article in Nature suggests what is needed in some human research. "Genomics research, in which researchers scan subjects' DNA in search of the genetic basis of many diseases, has focused too narrowly on studying subjects of European descent, write a team of genetics experts in the journal Nature this week."
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