Browsing by Author "Li, Sha"

Now showing 1 - 3 of 3
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    Emx2 underlies the development and evolution of marsupial gliding membranes
    (Springer Nature, 2024) Moreno, Jorge A.; Dudchenko, Olga; Feigin, Charles Y.; Mereby, Sarah A.; Chen, Zhuoxin; Ramos, Raul; Almet, Axel A.; Sen, Harsha; Brack, Benjamin J.; Johnson, Matthew R.; Li, Sha; Wang, Wei; Gaska, Jenna M.; Ploss, Alexander; Weisz, David; Omer, Arina D.; Yao, Weijie; Colaric, Zane; Kaur, Parwinder; Leger, Judy St; Nie, Qing; Mena, Alexandria; Flanagan, Joseph P.; Keller, Greta; Sanger, Thomas; Ostrow, Bruce; Plikus, Maksim V.; Kvon, Evgeny Z.; Aiden, Erez Lieberman; Mallarino, Ricardo; Center for Theoretical Biological Physics
    Phenotypic variation among species is a product of evolutionary changes to developmental programs1,2. However, how these changes generate novel morphological traits remains largely unclear. Here we studied the genomic and developmental basis of the mammalian gliding membrane, or patagium—an adaptative trait that has repeatedly evolved in different lineages, including in closely related marsupial species. Through comparative genomic analysis of 15 marsupial genomes, both from gliding and non-gliding species, we find that the Emx2 locus experienced lineage-specific patterns of accelerated cis-regulatory evolution in gliding species. By combining epigenomics, transcriptomics and in-pouch marsupial transgenics, we show that Emx2 is a critical upstream regulator of patagium development. Moreover, we identify different cis-regulatory elements that may be responsible for driving increased Emx2 expression levels in gliding species. Lastly, using mouse functional experiments, we find evidence that Emx2 expression patterns in gliders may have been modified from a pre-existing program found in all mammals. Together, our results suggest that patagia repeatedly originated through a process of convergent genomic evolution, whereby regulation of Emx2 was altered by distinct cis-regulatory elements in independently evolved species. Thus, different regulatory elements targeting the same key developmental gene may constitute an effective strategy by which natural selection has harnessed regulatory evolution in marsupial genomes to generate phenotypic novelty.
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    Galactose utilization
    (2021-11-16) San, Ka-yiu; Liu, Ping; Li, Sha; Rice University; United States Patent and Trademark Office
    The present disclosure describes a genetically engineered bacteria that relieves the catabolite repression problem exerted by the Spot 42 small regulatory RNA by adding a galactokinase that does not contain the Spot 42 binding region. As such, galK (galactokinase) and galM (mutarotase) and the like can be expressed allow better galactose utilization.
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    Molecular Basis of KAT2A Selecting Acyl-CoA Cofactors for Histone Modifications
    (AAAS, 2023) Li, Sha; Li, Nan; He, Jie; Zhou, Runxin; Lu, Zhimin; Tao, Yizhi Jane; Guo, Yusong R.; Wang, Yugang
    Emerging discoveries about undocumented acyltransferase activities of known histone acetyltransferases (HATs) advance our understandings in the regulation of histone modifications. However, the molecular basis of HATs selecting acyl coenzyme A (acyl-CoA) substrates for histone modification is less known. We here report that lysine acetyltransferase 2A (KAT2A) as an illustrative instance of HATs can selectively utilize acetyl-CoA, propionyl-CoA, butyryl-CoA, and succinyl-CoA to directly deposit 18 histone acylation hallmarks in nucleosome. By analyzing the co-crystal structures of the catalytic domain of KAT2A in complex with acetyl-CoA, propionyl-CoA, butyryl-CoA, malonyl-CoA, succinyl-CoA, and glutaryl-CoA, we conclude that the alternative substrate-binding pocket of KAT2A and the length and electrostatic features of the acyl chain cooperatively determine the selection of the acyl-CoA substrates by KAT2A. This study reveals the molecular basis underlying the pluripotency of HATs that selectively install acylation hallmarks in nucleosomes, which might serve as instrumental mechanism to precisely regulate histone acylation profiles in cells.