Chicago

Chicago

Center of the third largest metropolitan area in the United States; county seat of Cook County, Illinois, United States

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The Parliament of the World's Religions
April 9, 2021
www.prnewswire.com:443
/PRNewswire/ -- The Parliament of the World's Religions (PoWR), the world's premier interfaith convening, invites proposals for programs, presentations and...
The Associated Press
April 8, 2021
ABC News
The global shortage of semiconductors is forcing General Motors and Ford to further cut production at North American factories as chip supplies seem to be growing tighter
Dixon, G., Pan, H., Yang, D., Rosen, B. P., Jashari, T., Verma, N., Pulecio, J., Caspi, I., Lee, K., Stransky, S., Glezer, A., Liu, C., Rivas, M., Kumar, R., Lan, Y., Torregroza, I., He, C., Sidoli, S., Evans, T., Elemento, O., Huangfu, D.
April 9, 2021
Science
DNA methylation was one of the first epigenetic mechanisms discovered, but there is a limited understanding of its regulation and dysregulation in the context of development and disease. Dixon et al. performed a genome-wide CRISPR-Cas9 screen in human embryonic stem cells to identify DNA methylation regulators (see the Perspective by Gu and Goodell). A top screen hit, QSER1, proved to be essential for maintaining low methylation at DNA methylation valleys, which overlap with developmental genes and broad H3K27me3 and EZH2 peaks. Mechanistic examination revealed that QSER1 and the demethylating enzyme TET1 cooperate to safeguard developmental programs from de novo methylation by the enzyme DNMT3. Science , this issue p. [eabd0875][1]; see also p. [128][2] ### INTRODUCTION DNA methylation is essential to mammalian development, and dysregulation can cause serious pathological conditions, including immunodeficiency-centromeric instability-facial anomalies syndrome (ICF) and microcephalic dwarfism. The DNMT and TET enzymes are responsible for the addition and removal of DNA methylation, but how they coordinate to regulate the methylation landscape remains a central question. Using a knockin DNA methylation reporter, we performed a genome-wide CRISPR-Cas9 screen in human embryonic stem cells (hESCs) to discover DNA methylation regulators. ### RATIONALE We focused on bivalent promoters, defined by the presence of both active (H3K4me3) and repressive (H3K27me3) histone marks and typically occupied by Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2). In stem or progenitor cells, bivalent promoters are believed to maintain developmental regulators in a "poised state" ready for activation upon differentiation, and they are sensitive to DNA hypermethylation in dysfunctional cellular contexts such as cancer or aging. Creation of a knockin DNA methylation reporter line provided a singular opportunity to visualize epigenetic alterations otherwise "invisible" in terms of gene expression changes in the stem cell state. Using the bivalent PAX6 P0 promoter as a representative locus, we aimed to discover mechanisms that regulate DNA methylation at regions with similar chromatin features, which would inform not only gene regulation during development but also epigenetic dysregulation in disease. ### RESULTS Our screen successfully identified not only known methylation regulators such as TET1 , TDG , and KDM2B but also functionally uncharacterized genes, including QSER1 . Like the TET proteins, QSER1 safeguards bivalent promoters and poised enhancers (marked by H3K4me1 but not H3K27ac) against hypermethylation. However, distinct from the more general protective effect of the TET proteins on regulatory regions, QSER1 preferentially protects broad PRC2-bound and H3K27me3-marked regions and DNA methylation valleys (DMVs). Also known as DNA methylation canyons, DMVs identify large (≥5 kb) hypomethylated regions present in cells of many lineages and conserved across vertebrates. They are enriched with bivalent promoters, developmental genes, and transcription factors, including PAX6 and the HOX genes. QSER1 and TET1 showed high correlation in genomic occupancy measured by chromatin immunoprecipitation sequencing (ChIP-seq) and both were high at DMVs, whereas the binding of de novo methyltransferases DNMT3A and DNMT3B was excluded in DMVs and relatively enriched in the flanking regions. Further proteomic and genomic analyses revealed that QSER1 and TET1 share many common interacting proteins, depend on each other for efficient recruitment to DNA, and cooperate to limit the encroachment of DNMT3A and DNMT3B in DMVs. In addition, deleting DNMT3B reversed the hypermethylation in QSER1 knockout (KO) hESCs. Furthermore, combined KO of QSER 1 and TET1 had a stronger impact on DNA methylation and gene expression than either single KO and resulted in a failure of hESC differentiation to PDX1+NKX6.1+ pancreatic progenitors. ### CONCLUSION We show that QSER1 cooperates with TET1 to safeguard transcriptional and developmental programs from DNMT3-mediated de novo methylation at important genomic loci, especially in DMVs and bivalent promoters where hypermethylation has been linked to developmental disorders and cancers. Our work provides mechanistic insight into the region-specific regulation of the TET pathway and highlights the utility of unbiased genome-wide screens and locus-specific epigenetic measurements, including, but not limited to, DNA methylation for probing the epigenetic regulatory mechanisms relevant to human health. ![Figure][3] QSER1 safeguards DNA methylation valleys from de novo methylation. A fluorescence reporter hESC line (indicated by the red outline for fluorescence) was generated to track DNA methylation levels of the PAX6 promoter region in a genome-scale CRISPR-Cas9 screen for regulators of DNA methylation. A top screen hit, QSER1, cooperates with TET1 to antagonize DNMT3-mediated de novo methylation (depicted by the purple shading) at DMVs. DNA methylation is essential to mammalian development, and dysregulation can cause serious pathological conditions. Key enzymes responsible for deposition and removal of DNA methylation are known, but how they cooperate to regulate the methylation landscape remains a central question. Using a knockin DNA methylation reporter, we performed a genome-wide CRISPR-Cas9 screen in human embryonic stem cells to discover DNA methylation regulators. The top screen hit was an uncharacterized gene, QSER1 , which proved to be a key guardian of bivalent promoters and poised enhancers of developmental genes, especially those residing in DNA methylation valleys (or canyons). We further demonstrate genetic and biochemical interactions of QSER1 and TET1, supporting their cooperation to safeguard transcriptional and developmental programs from DNMT3-mediated de novo methylation. [1]: /lookup/doi/10.1126/science.abd0875 [2]: /lookup/doi/10.1126/science.abh3187 [3]: pending:yes
Helen Briggs - BBC science correspondent
April 8, 2021
news.yahoo.com
Scientists reveal how male gorillas tell others how big and strong they are by chest beating.
Cardiff Oncology, Inc.
April 8, 2021
www.prnewswire.com:443
/PRNewswire/ -- Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company developing onvansertib to treat cancers with the greatest medical...
BioSpace
April 7, 2021
BioSpace
The U.S. Department of Energy's Argonne National Laboratory is a founding partner of Duality, the first program in the nation that is dedicated to accelerating startup companies focused on quantum science and technology -- a rapidly emerging area that is poised to drive transformative advances across multiple industries.
Tom Redburn
April 6, 2021
www.nytimes.com
His insights on global finance earned him a Nobel, while his more iconoclastic theories fostered the adoption of a single European currency and supply-side economics.
The Economist
February 13, 2021
The Economist
The AAAS heard how cities with lower carbon emissions could be built
Jason Cross
April 7, 2021
Macworld
Apple has a lot of original content on the way for its subscription streaming video service. Here's what you'll soon (and eventually) be able to watch.
C. Brandon Ogbunu
April 1, 2021
Wired
Over the last year, the scientific community has been reluctant to openly discuss its missteps. But coming clean could help prevent the next pandemic.
Mark E. Bergen
March 26, 2021
Harvard Business Review
Algorithms should optimize for more than just profits.
March 17, 2021
WebWire
Apple's newly completed renewable projects, part of the company's planned $4.7 billion Green Bond spend, are bringing clean energy to local communities while reducing carbon emissions. In 2020, Apple funded 17 Green Bond projects that will avoid an average of 921,000 metric tons of carbon emissions annually, which is equivalent to removing nearly 200,000 cars from the road. The projects will generate 1.2 gigawatts of renewable energy globally, with Apple adding over 350 megawatts of newly...
Linda Jacobson
March 15, 2021
the Guardian
From a lack of broadband in Appalachia to obsolete devices distributed to poor urban families, the absence of reliable internet has meant a year of lost learning
Continental Who's Who
March 10, 2021
www.prnewswire.com:443
/PRNewswire/ -- Karen K. Slabas, MD, FACOG, is being recognized by Continental Who's Who as a Top Leading Gynecologist in the field of Medicine for her...
March 9, 2021
WebWire
The City of Chicago has selected Englewood Connect, a project by designers Skidmore, Owings, & Merrill (SOM) and TnS Studio, lead developer McLaurin Development Partners, and Farpoint Development, to create an incubator for small businesses and entrepreneurs in the city's Englewood neighborhood. As part of Mayor Lightfoot's INVEST South/West initiative, Englewood Connect will expand upon recent neighborhood investments to create a local commerce and culinary ecosystem, greater connectiv...
vipHomeLink
March 8, 2021
www.prnewswire.com:443
/PRNewswire/ -- vipHomeLink announces the acquisition of My Home Expert, a privately-held preventative home maintenance company founded in 2016 and based in...
DoorDash
March 8, 2021
www.prnewswire.com:443
/PRNewswire/ -- Today, DoorDash announced Made by Women, an in-app and digital platform that aims to champion women-owned businesses and uplift women voices,...
Turtle Wax
March 5, 2021
www.prnewswire.com:443
/PRNewswire/ -- The original car wax that put Turtle Wax® on the map was developed in founder Ben Hirsch's bathtub. The company at that time was called...
Erica Sweeney
March 4, 2021
Business Insider
Denver, Atlanta, and Raleigh-Durham are some of the cities tackling the digital divide and making big strides in innovation and sustainability.
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