{"id":469088,"date":"2026-05-05T06:24:18","date_gmt":"2026-05-05T06:24:18","guid":{"rendered":"https:\/\/www.europesays.com\/ie\/469088\/"},"modified":"2026-05-05T06:24:18","modified_gmt":"2026-05-05T06:24:18","slug":"gene-syntax-determines-dna-supercoiling-and-modulates-gene-expression","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/ie\/469088\/","title":{"rendered":"Gene Syntax Determines DNA Supercoiling and Modulates Gene Expression"},"content":{"rendered":"

\"\"<\/a>Digital DNA molecule, structure. Concept binary code human genome. DNA molecule with modified genes, 3D illustration<\/p>\n

When synthetic biologists sketch gene circuits, they usually think in terms of promoters, repressors, and transcription factors\u2014biochemical parts that toggle genes on or off. But DNA is not a flat schematic. It\u2019s a physical polymer that twists, coils, and buckles as genes are transcribed. A pair of new papers from MIT and collaborators shows that this physicality could suggest approaches to controlling the output of gene circuits.<\/p>\n

In a recent Science study titled \u201cGene syntax defines supercoiling-mediated transcriptional feedback<\/a>,\u201d researchers demonstrate that the order and orientation of neighboring genes\u2014what they call gene syntax\u2014can reshape local DNA supercoiling and, in turn, amplify or suppress the expression of adjacent genes.<\/p>\n

\u201cSyntax will be really useful for dynamic circuits. Now we have the ability to select not only the biochemistry of circuits, but also the physical design to support dynamics,\u201d said Katie Galloway, PhD, an assistant professor of chemical engineering at MIT.<\/p>\n

The team engineered human cell lines and hiPSCs with synthetic two\u2011gene reporter circuits arranged in tandem, divergent, or convergent configurations. Their earlier modeling predicted that divergent syntax should boost the expression of both genes, while tandem syntax should suppress the downstream gene. \u201cThe thing that we were trying to solve in this paper was: When you put two genes on the same piece of DNA, how does their physical interaction become coupled?\u201d said Galloway. The experimental results matched those predictions: divergent circuits amplified both genes, while tandem circuits showed strong upstream\u2011to\u2011downstream repression, with effects reaching up to 25\u2011fold.<\/p>\n

To understand why, the researchers used Region Capture Micro\u2011C, a high\u2011resolution genome\u2011folding mapping technique, to visualize how transcription reshapes DNA. When a gene was activated, the DNA downstream tightened into plectonemes\u2014twisted structures that hinder RNA polymerase binding\u2014while upstream DNA loosened. \u201cSupercoiling impacts transcription of adjacent genes by altering RNA polymerase binding, forming a feedback loop,\u201d the authors of the first paper wrote.<\/p>\n

The second paper, published in Nature Biomedical Engineering and titled \u201cSTRAIGHT-IN Dual: a platform for dual single-copy integrations of DNA payloads and gene circuits into human induced pluripotent stem cells<\/a>,\u201d introduced STRAIGHT\u2011IN Dual, a platform that enables simultaneous, allele\u2011specific, single\u2011copy integration of two DNA constructs into hiPSCs. This system allowed the team to \u201cinvestigate how promoter choice and gene syntax influence transgene silencing and how these design features affect reporter expression and forward programming of hiPSCs into neurons, motor neurons, and endothelial cells,\u201d according to the authors of the second paper.<\/p>\n

Using STRAIGHT\u2011IN Dual, the researchers also demonstrated a practical application: a divergent circuit expressing two components of a yellow fever antibody produced higher output than other configurations.<\/p>\n

\u201cThis is really exciting because we can coordinate gene expression in ways that just weren\u2019t possible before,\u201d Galloway said. \u201cNow that we understand the syntax, I think this will pave the way for us to program dynamic behaviors.<\/p>\n

\u201cIf you want coordinated expression, a divergent circuit is great. If you want something that\u2019s either\/or, you can imagine using a convergent or tandem circuit, so when one turns on, the other turns off, and you can alternate pulses,\u201d Galloway added.<\/p>\n","protected":false},"excerpt":{"rendered":"Digital DNA molecule, structure. Concept binary code human genome. DNA molecule with modified genes, 3D illustration When synthetic…\n","protected":false},"author":2,"featured_media":469089,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[77],"tags":[3286,18,7341,48415,11140,19,17,5,7173,133,205861,205860],"class_list":{"0":"post-469088","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-science","8":"tag-dna","9":"tag-eire","10":"tag-gene-expression","11":"tag-gene-regulation","12":"tag-genome-editing","13":"tag-ie","14":"tag-ireland","15":"tag-news","16":"tag-rna","17":"tag-science","18":"tag-straightu2011in-dual","19":"tag-transcription-factor"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ie\/116520541792227105","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/469088","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=469088"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/469088\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/469089"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=469088"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=469088"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=469088"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}