FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3158459025> ?p ?o ?g. }

• W3158459025 abstract "Gene activator proteins comprise distinct DNA-binding and transcriptional activation domains (ADs). Because few ADs have been described, we tested domains tiling all yeast transcription factors for activation in vivo and identified 150 ADs. By mRNA display, we showed that 73% of ADs bound the Med15 subunit of Mediator, and that binding strength was correlated with activation. AD-Mediator interaction in vitro was unaffected by a large excess of free activator protein, pointing to a dynamic mechanism of interaction. Structural modeling showed that ADs interact with Med15 without shape complementarity ('fuzzy' binding). ADs shared no sequence motifs, but mutagenesis revealed biochemical and structural constraints. Finally, a neural network trained on AD sequences accurately predicted ADs in human proteins and in other yeast proteins, including chromosomal proteins and chromatin remodeling complexes. These findings solve the longstanding enigma of AD structure and function and provide a rationale for their role in biology.Cells adapt and respond to changes by regulating the activity of their genes. To turn genes on or off, they use a family of proteins called transcription factors. Transcription factors influence specific but overlapping groups of genes, so that each gene is controlled by several transcription factors that act together like a dimmer switch to regulate gene activity. The presence of transcription factors attracts proteins such as the Mediator complex, which activates genes by gathering the protein machines that read the genes. The more transcription factors are found near a specific gene, the more strongly they attract Mediator and the more active the gene is. A specific region on the transcription factor called the activation domain is necessary for this process. The biochemical sequences of these domains vary greatly between species, yet activation domains from, for example, yeast and human proteins are often interchangeable. To understand why this is the case, Sanborn et al. analyzed the genome of baker’s yeast and identified 150 activation domains, each very different in sequence. Three-quarters of them bound to a subunit of the Mediator complex called Med15. Sanborn et al. then developed a machine learning algorithm to predict activation domains in both yeast and humans. This algorithm also showed that negatively charged and greasy regions on the activation domains were essential to be activated by the Mediator complex. Further analyses revealed that activation domains used different poses to bind multiple sites on Med15, a behavior known as ‘fuzzy’ binding. This creates a high overall affinity even though the binding strength at each individual site is low, enabling the protein complexes to remain dynamic. These weak interactions together permit fine control over the activity of several genes, allowing cells to respond quickly and precisely to many changes. The computer algorithm used here provides a new way to identify activation domains across species and could improve our understanding of how living things grow, adapt and evolve. It could also give new insights into mechanisms of disease, particularly cancer, where transcription factors are often faulty." @default.
• W3158459025 created "2021-05-10" @default.
• W3158459025 creator A5004683234 @default.
• W3158459025 creator A5010028459 @default.
• W3158459025 creator A5045278359 @default.
• W3158459025 creator A5047492229 @default.
• W3158459025 creator A5061322136 @default.
• W3158459025 creator A5065863381 @default.
• W3158459025 creator A5080046207 @default.
• W3158459025 creator A5088091669 @default.
• W3158459025 date "2021-04-27" @default.
• W3158459025 modified "2023-10-01" @default.
• W3158459025 title "Simple biochemical features underlie transcriptional activation domain diversity and dynamic, fuzzy binding to Mediator" @default.
• W3158459025 cites W1525178364 @default.
• W3158459025 cites W1543816617 @default.
• W3158459025 cites W1562712572 @default.
• W3158459025 cites W1761484484 @default.
• W3158459025 cites W1831401007 @default.
• W3158459025 cites W1958059146 @default.
• W3158459025 cites W1967616250 @default.
• W3158459025 cites W1971578941 @default.
• W3158459025 cites W1972043325 @default.
• W3158459025 cites W1975949180 @default.
• W3158459025 cites W1982756681 @default.
• W3158459025 cites W1984325151 @default.
• W3158459025 cites W1986156026 @default.
• W3158459025 cites W1992428272 @default.
• W3158459025 cites W1992797971 @default.
• W3158459025 cites W2000678537 @default.
• W3158459025 cites W2002662963 @default.
• W3158459025 cites W2006164030 @default.
• W3158459025 cites W2008708467 @default.
• W3158459025 cites W2009654808 @default.
• W3158459025 cites W2013593586 @default.
• W3158459025 cites W2017153232 @default.
• W3158459025 cites W2018531650 @default.
• W3158459025 cites W2019195942 @default.
• W3158459025 cites W2023487073 @default.
• W3158459025 cites W2024103356 @default.
• W3158459025 cites W2026593599 @default.
• W3158459025 cites W2027592091 @default.
• W3158459025 cites W2029099543 @default.
• W3158459025 cites W2036897871 @default.
• W3158459025 cites W2037546400 @default.
• W3158459025 cites W2040734916 @default.
• W3158459025 cites W2045362835 @default.
• W3158459025 cites W2047189513 @default.
• W3158459025 cites W2048284172 @default.
• W3158459025 cites W2053095043 @default.
• W3158459025 cites W2058870507 @default.
• W3158459025 cites W2060484288 @default.
• W3158459025 cites W2062439115 @default.
• W3158459025 cites W2068577315 @default.
• W3158459025 cites W2070083583 @default.
• W3158459025 cites W2070181970 @default.
• W3158459025 cites W2072354358 @default.
• W3158459025 cites W2078472628 @default.
• W3158459025 cites W2079760969 @default.
• W3158459025 cites W2081062649 @default.
• W3158459025 cites W2086660631 @default.
• W3158459025 cites W2091160336 @default.
• W3158459025 cites W2094775025 @default.
• W3158459025 cites W2097175728 @default.
• W3158459025 cites W2101248266 @default.
• W3158459025 cites W2102342920 @default.
• W3158459025 cites W2103017472 @default.
• W3158459025 cites W2111765755 @default.
• W3158459025 cites W2113235165 @default.
• W3158459025 cites W2114694204 @default.
• W3158459025 cites W2130479394 @default.
• W3158459025 cites W2131770328 @default.
• W3158459025 cites W2138141821 @default.
• W3158459025 cites W2139146047 @default.
• W3158459025 cites W2153187042 @default.
• W3158459025 cites W2157613837 @default.
• W3158459025 cites W2164099611 @default.
• W3158459025 cites W2165724034 @default.
• W3158459025 cites W2166871205 @default.
• W3158459025 cites W2168365185 @default.
• W3158459025 cites W2169333620 @default.
• W3158459025 cites W2170563234 @default.
• W3158459025 cites W2171722004 @default.
• W3158459025 cites W2175853567 @default.
• W3158459025 cites W2201713963 @default.
• W3158459025 cites W2204875887 @default.
• W3158459025 cites W2253581743 @default.
• W3158459025 cites W2345512687 @default.
• W3158459025 cites W2461977200 @default.
• W3158459025 cites W2468097647 @default.
• W3158459025 cites W2515162953 @default.
• W3158459025 cites W2554574275 @default.
• W3158459025 cites W2586373162 @default.
• W3158459025 cites W2591426128 @default.
• W3158459025 cites W2735621019 @default.
• W3158459025 cites W2755920386 @default.
• W3158459025 cites W2791474337 @default.
• W3158459025 cites W2792800146 @default.
• W3158459025 cites W2803006006 @default.
• W3158459025 cites W2806884808 @default.
• W3158459025 cites W2808847099 @default.

• next