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Chemical probes of epigenetic ‘readers’ of histone post-translational modifications (PTMs) have become powerful tools for mechanistic and functional studies of their target proteins in normal physiology and disease pathogenesis. Here we report the development of the first class of chemical probes of YEATS domains, newly identified ‘readers’ of histone lysine acetylation (Kac) and crotonylation (Kcr). Guided by the structural analysis of a YEATS–Kcr complex, we developed a series of peptide-based inhibitors of YEATS domains by targeting a unique π-π-π stacking interaction at the proteins’ Kcr recognition site. Further structure optimization resulted in the selective inhibitors preferentially binding to individual YEATS-containing proteins including AF9 and ENL with submicromolar affinities. We demonstrate that one of the ENL YEATS-selective inhibitors, XL-13m, engages with endogenous ENL, perturbs the recruitment of ENL onto chromatin, and synergizes the BET and DOT1L inhibition-induced downregulation of oncogenes in MLL-rearranged acute leukemia.

Adapting the framework of dependency theory, the article asks how the economic dependency of less developed countries (LDCs) on developed countries (DCs) is created through free trade. This article uses South Korea’s entry into the World Trade Organization (WTO) as a case study to illustrate this economic dependency creation process. Based on second-hand data from existing studies, the European Union, and the WTO, this article finds: (i) due to limited farmland size and high production costs, South Korean agricultural products cannot win a seat in the world market; (ii) the local agricultural sector was destroyed in South Korea because small farmers cannot earn a living by farming; and (iii) since the local agricultural sector cannot support the food demand in South Korea, South Korea now has to import a large amount of food. This article concludes that free trade actually destroys the local agricultural industry and the food security of South Korea, and consequently makes South Korea have to rely heavily on DCs for food import.