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Category: genetics – Page 490

Chromatin proteins have expanded the mammalian synthetic biology toolbox by enabling control of active and silenced states at endogenous genes. Others have reported synthetic proteins that bind DNA and regulate genes by altering chromatin marks, such as histone modifications. Previously we reported the first synthetic transcriptional activator, the “Polycomb-based transcription factor” (PcTF), that reads histone modifications through a protein-protein interaction between the PCD motif and trimethylated lysine 27 of histone H3 (H3K27me3). Here, we describe the genome-wide behavior of PcTF. Transcriptome and chromatin profiling revealed PcTF-sensitive promoter regions marked by proximal PcTF and distal H3K27me3 binding. These results illuminate a mechanism in which PcTF interactions bridge epigenetic marks with the transcription initiation complex. In three cancer-derived human cell lines tested here, many PcTF-sensitive genes encode developmental regulators and tumor suppressors. Thus, PcTF represents a powerful new fusion-protein-based method for cancer research and treatment where silencing marks are translated into direct gene activation.

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OAHU, HAWAI’I —(ENEWSPF)–September 1, 2016. As thousands of government representatives and conservationists convene in Oahu this week for the 2016 World Conservation Congress, international conservation and environmental leaders are raising awareness about the potentially dangerous use of gene drives — a controversial new synthetic biology technology intended to deliberately cause targeted species to become extinct.

Members of the International Union for the Conservation of Nature (IUCN), including NGOs, government representatives, and scientific and academic institutions, overwhelmingly voted to adopt a de facto moratorium on supporting or endorsing research into gene drives for conservation or other purposes until the IUCN has fully assessed their impacts. News of the August 26 digital vote comes as an important open letter to the group is being delivered.

Scientists and environmental experts and organizations from around the globe have advocated for a halt to proposals for the use of gene drive technologies in conservation. Announced today, a long list of environmental leaders, including Dr. Jane Goodall, DBE, genetics professor and broadcaster Dr. David Suzuki, Dr. Fritjof Capra, entomologist Dr. Angelika Hilbeck, Indian environmental activist Dr. Vandana Shiva and organic pioneer and biologist Nell Newman, have lent their support to the open letter: “A Call for Conservation with a Conscience: No Place for Gene Drives in Conservation.” The letter states, in part: “Gene drives, which have not been tested for unintended consequences, nor fully evaluated for ethical and social impacts, should not be promoted as conservation tools.”

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Cancer thrives when mutated cells undergo frequent division. Most anti-cancer drugs work by inserting themselves in between the DNA base pairs that encode our genetic information. This process is known as intercalation, and it can result in subtle changes to the DNA molecule’s geometric shape or tertiary structure. These structural changes interfere with the DNA’s transcription and a cell’s replication process, ultimately resulting in cell death.

While intercalating agents used in chemotherapy drugs are highly effective in fighting cancer, they also may kill important cells in the body and lead to other complications such as heart failure. Therefore, researchers are always searching for faster, cheaper and more accurate tools to aid in the design of next-generation anti-cancer drugs with reduced side effects.

A paper published in ACS Nano, one of the top nanotechnology journals in the world, explores this topic. “Modeling and Analysis of Intercalant Effects on Circular DNA Conformation,” (LINK TO http://pubs.acs.org/doi/abs/10.1021/acsnano.6b04876) focuses on the effect of the intercalating agent ethidium bromide (a mimic for many chemotherapy drugs) on the tertiary structure of DNA.

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Experts may reassure us that artificial intelligence won’t take over the world anytime soon – but they just might invade the multiplex.

At least that’s the plot developing at IBM, where the Watson artificial-intelligence team programmed a computer to come up with a scary trailer for “Morgan,” a thriller about a genetically modified, AI-enhanced super-human.

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It’s an add-on for CRISPR.

Researchers have created a new genome editing technique called Target-AID, which induces point mutations instead of cutting DNA

Gene editing technology has fantastic potential, but there are remaining issues and questions over safety and specificity. The major contender is currently CRISPR-Cas9, but this induces a double stranded break in DNA which is a slightly riskier approach — particularly if it cuts in other locations too that you don’t want it to. Research teams across the world are both optimising and customising the CRISPR system; creating more accurate versions or versions that regulate gene expression as opposed to editing it. One such team has now built an add-on to CRISPR, Target-AID.

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Dr Haroldo Silva from SENS talks about ALT cancer in this short film.

As normal cells divide, the ends of their chromosomes (telomeres) progressively shorten until eventually the cells reach senescence or undergo apoptosis. Cancers, which disproportionally kill more individuals in the 65 years or above age group, often overcome this built-in replication limit by expressing the enzyme telomerase.

However, about 10–15% cancers do not use telomerase and at least a major subset of these exhibit hallmarks of Alternative Lengthening of Telomeres (ALT) activity, including long and heterogeneous telomere lengths, presence of ALT-associated PML nuclear bodies (APBs), and generation of high-levels of C-rich circular telomeric DNA repeats (C-circles). Although there are many telomerase-based anti-cancer therapies in clinical development at the moment, research on ALT has not produced any promising therapies so far. This lag is due in part to a lack of assays that are reliable and amenable to high-content/high-throughput (HTS) screens.

Continue reading “Uncovering the genetic basis of ALT (Alternative Lengthening of Telomeres) — Harold Silva” | >