https://scholar.dgist.ac.kr/handle/20.500.11750/60124 2026-08-14T09:01:34Z https://scholar.dgist.ac.kr/handle/20.500.11750/60510 Title: Multivalent interactions mediate SNAIL transcription factor stimulation of the nucleosome deacetylase activity of the CoREST complex Author(s): Nam, Eunju; Valeriano, Manuel Osorio; Wang, Zhipeng A.; Whedon, Samuel D.; Jiang, Hanjie; Zhang, Maggie Xinran; DuBois-Coyne, Sarah; Haque, Ishraq A.; Jiang, Jennifer; Ferreira, Jennifer; Farnung, Lucas; Lee, Kwangwoon; Cole, Philip A. Abstract: SNAIL is a transcription factor that plays a role in development and cancer. SNAIL contains an N-terminal SNAG domain that is a high-affinity ligand for the histone substrate binding lysine-specific demethylase 1 (LSD1). SNAIL also contains a C-terminal zinc finger domain that binds to DNA E-box sequences. SNAIL and related transcription factor family members are known to recruit LSD1-containing protein complexes to specific sites in chromatin to regulate gene expression. LSD1 can form a multiprotein complex with histone deacetylase 1 (HDAC1) and CoREST scaffolding protein (LHC). In this study, we use a purified system to analyze the role of SNAIL in modulating nucleosome deacetylation by the LHC complex. We find that SNAIL enhances nucleosome deacetylase activity of the LHC complex at multiple histone H3 sites through multivalent interactions. Enhanced nucleosome deacetylation is dependent on SNAIL's SNAG and zinc finger domains. Unexpectedly, we find that SNAIL-stimulated nucleosome deacetylation by LHC also involves interactions of the nucleosome histone acidic patch, including histone H2A acidic residues. Modeling and mutagenesis experiments suggest that this acidic patch could engage a basic patch in the disordered segment of LSD1. Together, these findings reveal how a transcription factor can influence a cascade of molecular recognition events to regulate chromatin structure. 2026-06-30T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60389 Title: Histone modification cross-talk: analytical tools and molecular mechanisms Author(s): Jiang, Jennifer; DuBois-Coyne, Sarah; Nam, Eunju; Whedon, Samuel D.; Lee, Kwangwoon; Cole, Philip A. Abstract: Chromatin function emerges from combinatorial patterns of histone post-translational modifications (PTMs) that are read, written, and erased by dedicated enzymes. Over the past 30years, increasing evidence suggests that specific histone PTMs or combinations of PTMs influence one another, constituting epigenetic cross-talk that shapes chromatin structure, protein-protein interactions, and catalytic efficiency of nucleosome-targeting enzymes. Here, we summarize mechanistic and methodological advances that enable rigorous interrogation of histone PTM interplay. We highlight selected nucleosome engineering strategies that build precisely modified substrates to test in vitro, proteomic pipelines that preserve combinatorial information, and omics technology that can globally profile integrated chromatin regulatory events in cells and tissues. Furthermore, we survey multivalent reader modules and engineered biosensors that report combinatorial marks in nucleosomes and living cells. Representative case studies illustrate how defined PTMs modulate catalytic parameters of writer and eraser complexes, including lysine methyltransferases, demethylases, acetyltransferases, and deacetylases, focusing on cross-talk with histone H3 N-terminal tail marks. These include the role of H3K9me2/3 and K14ac in directing propagation of H3K9me3, the role of H3K4me1/2 and K14ac in slowing H3K4 demethylation, the role of H3K4me2/3 in directing H3K9 acetylation, and the role of H3K36 methylation in directing deacetylation of H3 and H4. The substrates for these case studies include both mononucleosomes and nucleosome arrays. These examples illustrate the principle of epigenetic cross-talk, namely, that specific combinatorial PTMs can affect enzymes and alter local biochemistry. 2026-04-30T15:00:00Z