Hyoung-Pyo Kim

Hyejin Kim, Sun-Ho Lee, Chul Min Yang, Eun-Chong Lee, Ru-Ri Lee, Seunghyun Lee & Hyoung-Pyo Kim. BMB Reports 2026;59:482-92. https://doi.org/10.5483/BMBRep.2026-0119

Endoplasmic reticulum (ER) stress triggers transcriptional programs that promote either adaptation or apoptosis, yet the epigenetic mechanisms underlying this response remain incompletely understood. Here, integrated multi-omics analyses of unfolded protein response transcription factor knockout cells identify ATF4 as a dominant regulator of ER stress-responsive enhancer activation and chromatin looping. Loss of ATF4 markedly impairs stress-induced H3K27ac accumulation and enhancer–promoter interactions at ATF4-associated regulatory elements, establishing ATF4 as a central organizer of the stress-responsive regulatory landscape. We further identify CHOP as a key functional partner of ATF4 during ER stress. Integrative analyses of ATF4 occupancy and H3K27ac landscapes in CHOP-knockout cells reveal that CHOP selectively modulates ATF4-dependent enhancer activity and controls distinct subsets of stress-responsive genes. This cooperation preferentially promotes apoptosis-associated transcriptional programs while having limited effects on core adaptive responses. Together, our findings define a hierarchical regulatory framework in which ATF4 establishes enhancer activation and chromatin looping networks, whereas CHOP selectively diversifies their output to specify ER stress-responsive gene programs.

CTCF (CCCTC-binding factor) is crucial for organizing mammalian genomes into domains and structural loops, yet its role in enhancer–promoter interactions remains unclear. Here, we demonstrate that 3D enhancer architecture undergoes marked reorganization upon CTCF depletion in activated CD4+ T cells. Despite this, active transcription, particularly driven by STAT5-bound super-enhancers, maintains enhancer loops independently of CTCF. Interestingly, robust enhancer–promoter interactions are associated with the release of RNA polymerase II (RNAPII) pausing and require CTCF-dependent 3D genome organization to shape immune-related gene expression patterns in CD4+ T cells. Notably, CTCF depletion reprograms the transcriptional response of CD4+ T cells to JAK inhibitors by rewiring the STAT5 enhancer network rather than altering the upstream JAK/STAT signaling cascade. This study emphasizes the role of 3D enhancer architecture orchestrated by CTCF and active transcription in directing precise cell identity gene expression through RNAPII pause-release in CD4+ T cells.

Min-Ji Song, Mikyoung Kim, Jieun Seo, Heon-Woo Kwon, Chang Hoon Yang, Jung-Sik Joo, Yong-Joon Cho & Hyoung-Pyo Kim. BMB Reports -0001;0:. https://doi.org/10.5483/BMBRep.2024-0175

Eun-Chong Lee, Kyungwoo Kim, Woong-Jae Jung & Hyoung-Pyo Kim. BMB Reports 2023;56:398-403. https://doi.org/10.5483/BMBRep.2023-0044

Dendritic cells are antigen-presenting cells orchestrating innate and adaptive immunity. The crucial role of transcription factors and histone modifications in the transcriptional regulation of dendritic cells has been extensively studied. However, it is not been well understood whether and how three-dimensional chromatin folding controls gene expression in dendritic cells. Here we demonstrate that activation of bone marrow-derived dendritic cells induces extensive reprogramming of chromatin looping as well as enhancer activity, both of which are implicated in the dynamic changes in gene expression. Interestingly, depletion of CTCF attenuates GM-CSF-mediated JAK2/STAT5 signaling, resulting in defective NF-κB activation. Moreover, CTCF is necessary for establishing NF-κB-dependent chromatin interactions and maximal expression of pro-inflammatory cytokines, which prime Th1 and Th17 cell differentiation. Collectively, our study provides mechanistic insights into how three-dimensional enhancer networks control gene expression during bone marrow-derived dendritic cells activation, and offers an integrative view of the complex activities of CTCF in the inflammatory response of bone marrow-derived dendritic cells.

CTCF is crucial to the organization of mammalian genomes into loop structures. According to recent studies, the transcription apparatus is compartmentalized and concentrated at super-enhancers to form phase-separated condensates and drive the expression of cell-identity genes. However, it remains unclear whether and how transcriptional condensates are coupled to higher-order chromatin organization. Here, we show that CTCF is essential for RNA polymerase II (Pol II)-mediated chromatin interactions, which occur as hyperconnected spatial clusters at super-enhancers. We also demonstrate that CTCF clustering, unlike Pol II clustering, is independent of liquid-liquid phase-separation and resistant to perturbation of transcription. Interestingly, clusters of Pol II, BRD4, and MED1 were found to dissolve upon CTCF depletion, but were reinstated upon restoration of CTCF, suggesting a potent instructive function for CTCF in the formation of transcriptional condensates. Overall, we provide evidence suggesting that CTCF-mediated chromatin looping acts as an architectural prerequisite for the assembly of phase-separated transcriptional condensates.

One of the most commonly used drugs in chemotherapy, 5‑fluorouracil (5‑FU) has been shown to be effective in only 10‑15% of patients with colon cancer. Thus, studies of the mechanisms affecting 5‑FU sensitivity in these patients are necessary. The tumor suppressor protein p53 is a transcription factor that serves important roles in cell apoptosis by regulating the cell cycle. It has also been characterized as a key factor influencing drug sensitivity. Furthermore, accessible chromatin is a hallmark of active DNA regulatory elements and functions as a crucial epigenetic factor regulating cancer mechanisms. The present study assessed the genetic regulatory landscape in colon cancer by performing RNA sequencing and Assay for Transposase‑Accessible Chromatin sequencing, and investigated the effects of 5‑FU on chromatin accessibility and gene expression. Notably, while treatment with 5‑FU mediated global increases in chromatin accessibility, chromatin organization in several genomic regions differed depending on the expression status of p53. Since the occupancy of p53 does not overlap with accessible chromatin regions, the 5‑FU‑mediated changes in chromatin accessibility were not regulated by direct binding of p53. In the p53‑expressing condition, the 5‑FU‑mediated accessible chromatin region was primarily associated with genes encoding cell death pathways. Additionally, 5‑FU was revealed to induce open chromatin conformation at regions containing binding motifs for AP‑1 family transcription factors, which may drive expression of apoptosis pathway genes. In conclusion, expression of p53 may confer 5‑FU sensitivity by regulating chromatin accessibility of distinct genes associated with cell apoptosis in a transcription‑independent manner.