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Uncovering key players in gene silencing: Insights into plant growth and human diseases – Phys.org

<div data-thumb="https://scx1.b-cdn.net/csz/news/tmb/2024/uncovering-key-players.jpg" data-src="https://scx2.b-cdn.net/gfx/news/hires/2024/uncovering-key-players.jpg" data-sub-html="A genetic suppressor screen identifies RdDM to be the major pathway for repeat expansion-induced epigenetic silencing. a, Phenotypes (denoted by their original screen identifiers) of the isolated suppressors compared to Bur-0. The irregularly impaired leaves are marked by white arrows in the Bur-0 wild type. Scale bars, 2 cm. b, Relative IIL1 expression levels in genetic suppressors identified through the genetic screen. The numbers represent the original screen identifiers, and the corresponding genes identified after cloning are shown below. Average expression levels based on three biological replicates for each line (except for Bur-0 and fug1, where n = 5 and 4, respectively) are shown. Asterisks (*) denote individual data points. P values are based on a one-way analysis of variance with Tukey’s post hoc test, and lines with different letters are significantly different from each other (P < 0.05). Error bars represent s.e.m. c, An example of SHOREmap analysis with 44-2 identifies a mutation in Pol V. High-frequency alleles (>0.85) are colored red, and red crosses show the putative causal alleles. Credit: Nature Plants (2024). DOI: 10.1038/s41477-024-01672-5″>

Uncovering key players in gene silencing: Insights into plant growth and human diseases
A genetic suppressor screen identifies RdDM to be the major pathway for repeat expansion-induced epigenetic silencing. a, Phenotypes (denoted by their original screen identifiers) of the isolated suppressors compared to Bur-0. The irregularly impaired leaves are marked by white arrows in the Bur-0 wild type. Scale bars, 2 cm. b, Relative IIL1 expression levels in genetic suppressors identified through the genetic screen. The numbers represent the original screen identifiers, and the corresponding genes identified after cloning are shown below. Average expression levels based on three biological replicates for each line (except for Bur-0 and fug1, where n = 5 and 4, respectively) are shown. Asterisks (*) denote individual data points. P values are based on a one-way analysis of variance with Tukey’s post hoc test, and lines with different letters are significantly different from each other (P < 0.05). Error bars represent s.e.m. c, An example of SHOREmap analysis with 44-2 identifies a mutation in Pol V. High-frequency alleles (>0.85) are colored red, and red crosses show the putative causal alleles. Credit: Nature Plants (2024). DOI: 10.1038/s41477-024-01672-5

Monash University biologists have shed light on the intricate molecular mechanisms that are responsible for gene silencing induced by expanded repeats in an international study published today in Nature Plants.

This phenomenon has been linked to a number of hereditary illnesses, including Friedreich’s ataxia in humans, and causes growth abnormalities in plants such as Arabidopsis thaliana.

The research aimed to understand the mechanism by which enlarged repeats cause epigenetic silencing, an essential procedure for controlling gene expression.

Discovering novel components that are necessary for this silencing process was accomplished by the researchers using a plant model that presents the symptoms of growth defects at higher temperatures but not at lower temperatures.

SUMO protease FUG1, histone reader AL3, and chromodomain LHP1 were identified as the three most important actors, according to the study.

“These proteins come together to create an essential module required for epigenetic silencing induced by repeat expansion,” said lead study author Dr. Sridevi Sureshkumar, who heads the Genetics at the Core Research Group at the Monash University School of Biological Sciences.

“Our research reveals the crucial role that these proteins play in orchestrating gene silencing that is triggered by expanded repeats,” Dr. Sureshkumar said.

“The awareness of these systems not only contributes to the advancement of our understanding of plant biology but also offers insights into diseases that affect humans,” she said.

During the course of the research, modern genetic screening methods and yeast two-hybrid tests were utilized in order to determine that FUG1, an uncharacterized SUMO protease, is a significant participant in epigenetic silencing. Following further analysis, it was shown that FUG1 interacts with AL3, which is a histone reader that is known to bind to particular histone marks that are related to effective .

In addition, the researchers found that the AL3 protein interacts with LHP1, which is a chromodomain protein that plays a role in the dissemination of restrictive histone marks. The reversal of gene silencing and the suppression of repeat expansion-associated symptoms were both brought about by the loss of function of any one of these components during the experiment.

“These findings highlight the importance of post-translational modifiers and histone readers in epigenetic regulation,” Dr. Sureshkumar said.

“Our study paves the way for further research into the role of these proteins in various biological processes and human diseases,” she said.

“The findings not only present potential consequences for human health but also contribute to our understanding of plant biology, which is already advanced.”

Dr. Sureshkumar, who led this international study involving Institutions in the UK, China, Canada, India, and Australia, said that multinational collaboration helped them make progress across diverse aspects of this research.

Dr. Sureshkumar said this research could potentially be a pathway for the development of novel therapeutic techniques that target epigenetic dysregulation in people who suffer from hereditary illnesses.

More information:
Sridevi Sureshkumar et al, SUMO protease FUG1, histone reader AL3 and chromodomain protein LHP1 are integral to repeat expansion-induced gene silencing in Arabidopsis thaliana, Nature Plants (2024). DOI: 10.1038/s41477-024-01672-5

Citation:
Uncovering key players in gene silencing: Insights into plant growth and human diseases (2024, April 19)
retrieved 19 April 2024
from https://phys.org/news/2024-04-uncovering-key-players-gene-silencing.html

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Microsoft was ‘very, very worried’ about Google and OpenAI in 2019 – Fortune

In 2019, Microsoft executives at the highest level had an anxious email exchange about AI that would ultimately kick-start its AI investment

Back then, chief technology officer Kevin Scott sent a four-page email to CEO Satya Nadella and cofounder Bill Gates with the subject line “thoughts on OpenAI,” which outlined his fears that Microsoft was falling drastically behind in the AI race. At the time, ChatGPT was still more than four years away from being released to the public. But even then, Scott realized OpenAI and Google had made extraordinary steps forward in their work on AI. 

“The thing that’s interesting about what OpenAI and DeepMind and Google Brain are doing is the scale of their ambition,” Scott wrote. 

The email, which is heavily redacted, came to light as part of the Justice Department’s antitrust investigation into Google and was first reported by Business Insider.  

That same year, Microsoft would invest $1 billion in OpenAI, the very company Scott cited in his email. Eventually the tech giant would go on to invest at least another $10 billion into the startup, which is credited for popularizing AI chatbots for everyday use with the launch of ChatGPT. The two companies are now intertwined. Microsoft brings its vast resources, the need for which Scott outlines in his email, while OpenAI brings its cutting-edge AI expertise that had so preoccupied the Microsoft executive. 

In his email, Scott says he miscalculated what exactly Google and OpenAI were trying to accomplish with their AI work. At the time, DeepMind, a startup owned by Google, was trying to build an AI system that could play the Chinese board game Go, which Scott seems to be referencing. 

“I was highly dismissive of that,” Scott wrote. “That was a mistake.”

Scott marveled at how Google and OpenAI had built an entire infrastructure around their AI push. In the email, he said he was surprised Google and OpenAI had designed data centers, sourced silicon chips, and built programming frameworks to enable all their work, according to the email. 

“When they took all of the infrastructure that they had built to build NLP [natural language processing] models that we couldn’t easily replicate, I started to take things more seriously,” Scott told Gates and Nadella. 

Microsoft did not respond to a request for comment.

The advent of AI has put many of those resources in extremely high demand. AI requires extraordinary amounts of computing power to both run and train the models behind chatbots like Google’s Gemini and OpenAI’s ChatGPT. Data centers have become hot properties both as tech investments and as real-estate assets, with some of the biggest investment firms racing to corner the market. Silicon chips, or semiconductors, went through an unprecedented shortage as more and more companies tried to hoard them, fearing they’d run out. Their importance is best exemplified by Nvidia’s legendary stock surge over the past year. AI models also necessitated vast amounts of cloud computing, which companies like Google and Microsoft invested heavily in over the past decade. 

But back in 2019, when he sent the email, Scott realized how important all these infrastructure upgrades were to developing the sort of AI that’s now commonplace. “As I dug in to try to understand where all of the capability gaps were between Google and us for model training, I got very, very worried,” Scott said. 

Scott says at the time that it took Microsoft about six months to train one of its AI models because “our infrastructure wasn’t up to the task.” 

Microsoft also realized it was lagging its competitors in terms of the personnel it had dedicated toward machine learning and AI research. Since then, employees well-versed in AI have found no shortage of job offers (some with million-dollar pay packages) from companies eager to hire them. The rush to hire AI talent would eventually spread beyond the tech sector to virtually every industry in the corporate world. 

Microsoft, according to Scott, had some “very smart” machine-learning experts, but they lacked the right resources and headcounts to make a notable dent in deep learning, the complex training mechanism used to develop AI models. That meant their work took longer than it should have, a worrying prospect amid the imminent AI arms race. “We are multiple years behind the competition in terms of [machine learning] scale,” Scott said. 

Meanwhile, Nadella seemed to take Scott’s extensive concerns to heart. Nadella cc’ed chief financial officer Amy Hood and replied: This is “why I want us to do this.”

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‘Fantastic Four’ Enlists Paul Walter Hauser – Hollywood Reporter

Paul Walter Hauser will be making his Marvel debut with a role in The Fantastic Four, The Hollywood Reporter has confirmed.

No character details were available, but he joins a cast that includes Pedro Pascal as Reed Richards/Mr. Fantastic, Vanessa Kirby as Sue Storm/The Invisible Woman, Joseph Quinn as Johnny Storm/The Human Torch, Ebon Moss-Bachrach as Ben Grimm/The Thing and Julia Garner as the Silver Surfer.

The feature has a July 25, 2025 release date and hails from WandaVision director Matt Shakman, with Eric Pearson writing the latest draft of the script. It centers on the characters created by Stan Lee and Jack Kirby for the comic book that launched the Marvel Comics universe in 1961.

Hauser has been on a role this week. He lined up work in Paramount’s Naked Gun reboot, while his Chris Farley biopic sold to New Line. He is known for his breakout work in I, Tonya (2017), with other credits including BlacKkKlansman (2018), Richard Jewell (2019) and Cruella (2021).

As for Marvel, the studio is gearing up for the release of Deadpool & Wolverine, with the Ryan Reynolds-Hugh Jackman two-hander arriving July 26.

Hauser is repped by CAA, Artists First, and Schreck Rose. Deadline first reported the news of his Fantastic Four casting.

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Trevoh Chalobah’s header puts Chelsea ahead of Tottenham | Premier League | NBC Sports – NBC Sports

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