Min Kyung Lee

All Publications

• Nutrient starvation-induced Hda1C rewiring: coordinated regulation of transcription and translation. Nucleic acids research Lee, M. K., Kang, B., Shin, M. K., Kim, Y. K., Kim, H. Y., Lee, S. Y., Roh, T. Y., Kim, T. 2025; 53 (7)

  Abstract

  In yeast, Hda1 histone deacetylase complex (Hda1C) plays an important role in transcriptional regulation by modulating histone acetylation. We here explored the changes in Hda1C binding in nutrient-rich and -starved conditions. Chromatin immunoprecipitation sequencing revealed that starvation alters RNA Pol II and Hda1C binding to coding genes in a highly correlated manner. Interestingly, we discovered RNA Pol II transcription-independent recruitment of Hda1C to intergenic regions, particularly the upstream regulatory sequences (URS) of ribosomal protein (RP) genes, which are enriched with Rap1 binding sites. Under nutrient starvation, Rap1 contributes to the recruitment of Hda1C to these URS regions, where Hda1C deacetylates histones, thereby fine-tuning basal gene expression and delaying RP gene reactivation. Furthermore, Hda1C is also required for RNA Pol I transcription of ribosomal RNAs (rRNAs) and RNA Pol III transcription of transfer RNA (tRNA) genes, especially in nutrient-limited conditions. Significantly, Hda1C mutants are sensitive to translation inhibitors and display altered ribosome profiles. Thus, Hda1C may coordinate transcriptional regulation within the nucleus with translation control in the cytoplasm and could be a key regulator of gene expression responses to nutrient stress.

  View details for DOI 10.1093/nar/gkaf256

  View details for PubMedID 40248913

  View details for PubMedCentralID PMC12006795

• Context-Dependent and Locus-Specific Role of H3K36 Methylation in Transcriptional Regulation. Journal of molecular biology Lee, M. K., Park, N. H., Lee, S. Y., Kim, T. 2025; 437 (1): 168796

  Abstract

  H3K36 methylation is a critical histone modification involved in transcription regulation. It involves the mono (H3K36me1), di (H3K36me2), and/or tri-methylation (H3K36me3) of lysine 36 on histone H3 by methyltransferases. In yeast, Set2 catalyzes all three methylation states. By contrast, in higher eukaryotes, at least eight methyltransferases catalyze different methylation states, including SETD2 for H3K36me3 and the NSD family for H3K36me2 in vivo. Both Set2 and SETD2 interact with the phosphorylated CTD of RNA Pol II, which links H3K36 methylation to transcription. In yeast, H3K36me3 and H3K36me2 peak at the 3' ends of genes. In higher eukaryotes, this is also true for H3K36me3 but not for H3K36me2, which is enriched at the 5' ends of genes and intergenic regions, suggesting that H3K36me2 and H3K36me3 may play different regulatory roles. Whether H3K36me1 demonstrates preferential distribution remains unclear. H3K36me3 is essential for inhibiting transcription elongation. It also suppresses cryptic transcription by promoting histone deacetylation by the histone deacetylases Rpd3S (yeast) and variant NuRD (higher eukaryotes). H3K36me3 also facilitates DNA methylation by DNMT3B, thereby preventing spurious transcription initiation. H3K36me3 not only represses transcription since it promotes the activation of mRNA and cryptic promoters in response to environmental changes by targeting the histone acetyltransferase NuA3 in yeast. Further research is needed to elucidate the methylation state- and locus-specific functions of H3K36me1 and the mechanisms that regulate it.

  View details for DOI 10.1016/j.jmb.2024.168796

  View details for PubMedID 39299382

• Core promoter activity contributes to chromatin-based regulation of internal cryptic promoters. Nucleic acids research Lee, B. B., Woo, H., Lee, M. K., Youn, S., Lee, S., Roe, J. S., Lee, S. Y., Kim, T. 2021; 49 (14): 8097-8109

  Abstract

  During RNA polymerase II (RNA Pol II) transcription, the chromatin structure undergoes dynamic changes, including opening and closing of the nucleosome to enhance transcription elongation and fidelity. These changes are mediated by transcription elongation factors, including Spt6, the FACT complex, and the Set2-Rpd3S HDAC pathway. These factors not only contribute to RNA Pol II elongation, reset the repressive chromatin structures after RNA Pol II has passed, thereby inhibiting aberrant transcription initiation from the internal cryptic promoters within gene bodies. Notably, the internal cryptic promoters of infrequently transcribed genes are sensitive to such chromatin-based regulation but those of hyperactive genes are not. To determine why, the weak core promoters of genes that generate cryptic transcripts in cells lacking transcription elongation factors (e.g. STE11) were replaced with those from more active genes. Interestingly, as core promoter activity increased, activation of internal cryptic promoter dropped. This associated with loss of active histone modifications at the internal cryptic promoter. Moreover, environmental changes and transcription elongation factor mutations that downregulated the core promoters of highly active genes concomitantly increased their cryptic transcription. We therefore propose that the chromatin-based regulation of internal cryptic promoters is mediated by core promoter strength as well as transcription elongation factors.

  View details for DOI 10.1093/nar/gkab639

  View details for PubMedID 34320189

  View details for PubMedCentralID PMC8373055

• Histone H4-Specific Deacetylation at Active Coding Regions by Hda1C. Molecules and cells Lee, M. K., Kim, T. 2020; 43 (10): 841-847

  Abstract

  Histone acetylation and deacetylation play central roles in the regulation of chromatin structure and transcription by RNA polymerase II (RNA Pol II). Although Hda1 histone deacetylase complex (Hda1C) is known to selectively deacetylate histone H3 and H2B to repress transcription, previous studies have suggested its potential roles in histone H4 deacetylation. Recently, we have shown that Hda1C has two distinct functions in histone deacetylation and transcription. Histone H4-specific deacetylation at highly transcribed genes negatively regulates RNA Pol II elongation and H3 deacetylation at inactive genes fine-tunes the kinetics of gene induction upon environmental changes. Here, we review the recent understandings of transcriptional regulation via histone deacetylation by Hda1C. In addition, we discuss the potential mechanisms for histone substrate switching by Hda1C, depending on transcriptional frequency and activity.

  View details for DOI 10.14348/molcells.2020.0141

  View details for PubMedID 32913143

  View details for PubMedCentralID PMC7604025

• Transcription-dependent targeting of Hda1C to hyperactive genes mediates H4-specific deacetylation in yeast. Nature communications Ha, S. D., Ham, S., Kim, M. Y., Kim, J. H., Jang, I., Lee, B. B., Lee, M. K., Hwang, J. T., Roh, T. Y., Kim, T. 2019; 10 (1): 4270

  Abstract

  In yeast, Hda1 histone deacetylase complex (Hda1C) preferentially deacetylates histones H3 and H2B, and functionally interacts with Tup1 to repress transcription. However, previous studies identified global increases in histone H4 acetylation in cells lacking Hda1, a component of Hda1C. Here, we find that Hda1C binds to hyperactive genes, likely via the interaction between the Arb2 domain of Hda1 and RNA polymerase II. Additionally, we report that Hda1C specifically deacetylates H4, but not H3, at hyperactive genes to partially inhibit elongation. This role is contrast to that of the Set2-Rpd3S pathway deacetylating histones at infrequently transcribed genes. We also find that Hda1C deacetylates H3 at inactive genes to delay the kinetics of gene induction. Therefore, in addition to fine-tuning of transcriptional response via H3-specific deacetylation, Hda1C may modulate elongation by specifically deacetylating H4 at highly transcribed regions.

  View details for DOI 10.1038/s41467-019-12077-w

  View details for PubMedID 31537788

  View details for PubMedCentralID PMC6753149