Biology subjects

Nakajima-Takagi, Y.

Publications and source records attributed to Nakajima-Takagi, Y..

3 recordsLinked to original sources

bioRxiv2026

Coffee remodels the global histone acetylation landscape with reduced H3K27ac at the MYC promoter

Coffee consumption has been associated with reduced risks of multiple chronic diseases, including cancer; however, whether coffee regulates the epigenetic landscape remains largely unknown. Here, we show that coffee extensively remodels the histone acetylation landscape in human cells. Quantitative histone modification proteomics revealed a global reduction in active histone acetylation marks following coffee treatment. Mechanistically, coffee reduced the abundance of the histone acetyltransferases GCN5 and MOF, decreased 14-3-3 proteins, promoted the nuclear accumulation of class II histone deacetylases, and induced histone hypoacetylation that was reversed by the histone deacetylase inhibitor trichostatin A. Genome-wide H3K27ac profiling revealed widespread loss of promoter and enhancer acetylation, accompanied by broad transcriptional reprogramming. Integrative analyses of ChIP-seq, RNA-seq, proteomics and biochemical validation consistently demonstrated suppression of the MYC transcriptional program, including reduced MYC expression, decreased H3K27ac at MYC target promoters, downregulation of canonical MYC target genes and attenuation of MYC target gene signatures. Functionally, coffee inhibited cancer cell proliferation with minimal cell death. Collectively, our findings identify whole coffee as a previously unrecognized epigenetic modulator that remodels the histone acetylation landscape in association with suppression of the MYC transcriptional program, providing a molecular framework for understanding the epigenetic basis underlying the anti-tumor effects of coffee.

molecular biology↗

bioRxiv2025

Niche-targeted therapy via YAP/TAZ activation enhances hematopoietic regeneration

The distinctive milieu of the bone marrow (BM), known as the BM niche, supports hematopoietic stem cells (HSCs) and serves as a foundation for hematopoietic regeneration. Myeloablative stress disrupts not only hematopoietic stem and progenitor cells but also essential BM niche components, including endothelial cells (ECs) and mesenchymal stromal cells (MSCs); disruption of the latter impairs efficient hematopoietic recovery. However, therapeutic strategies targeting niche restoration remain largely underdeveloped. Here, we demonstrate that the Hippo pathway effectors YAP/TAZ are critical for enabling ECs and MSCs to respond to BM injury, and that YAP/TAZ activation accelerates BM niche recovery, thereby promoting hematopoietic regeneration. We found that YAP/TAZ are rapidly activated in both MSCs and ECs following myeloablative stress, maintaining MSC multipotency and orchestrating vascular remodeling. Mechanistically, YAP/TAZ function as transcriptional hubs in MSCs, regulating key transcriptional factors such as Ebf1 and Ebf3. This regulation preserves MSC identity by preventing osteogenic and fibrogenic differentiation while promoting the expression of hematopoietic factors such as Cxcl12 and angiogenic factors. In parallel, YAP/TAZ signaling in ECs facilitates pro-angiogenic responses and drives sinusoidal vessel remodeling after injury. These YAP/TAZ-mediated niche responses are essential for HSC retention and hematopoietic regeneration following diverse myelosuppressive therapies. Notably, pharmacological activation of YAP/TAZ enhances BM niche reorganization and augments hematopoietic regeneration following myeloablative therapies. These findings establish YAP/TAZ as central regulators of BM niche resilience, providing a rationale for niche-targeted therapeutic strategies to enhance hematopoietic regeneration. Key points{blacksquare} YAP/TAZ enable BM niche cells to sense injury and restore their structure and function, thereby promoting hematopoietic regeneration. {blacksquare}Pharmacological activation of YAP/TAZ enhances BM niche resilience and accelerates hematopoietic recovery after myelosuppressive therapies.

cell biology↗

bioRxiv2022

Polycomb repressive complex 1.1 coordinates homeostatic and emergency myelopoiesis

Polycomb repressive complex (PRC) 1 regulates stem cell fate by mediating mono-ubiquitination of histone H2A at lysine 119. While canonical PRC1 is critical for hematopoietic stem and progenitor cell (HSPC) maintenance, the role of non-canonical PRC1 in hematopoiesis remains elusive. PRC1.1, a non-canonical PRC1, consists of PCGF1, RING1B, KDM2B, and BCOR. We recently showed that PRC1.1 insufficiency induced by the loss of PCGF1 or BCOR causes myeloid-biased hematopoiesis and promotes transformation of hematopoietic cells in mice. Here we show that PRC1.1 serves as an epigenetic switch that coordinates homeostatic and emergency hematopoiesis. PRC1.1 maintains balanced output of steady-state hematopoiesis by restricting C/EBP-dependent precocious myeloid differentiation of HSPCs and the HOXA9- and {beta}-catenin-driven self-renewing network in myeloid progenitors. Upon regeneration, PRC1.1 is transiently inhibited to facilitate formation of granulocyte-macrophage progenitor (GMP) clusters, thereby promoting emergency myelopoiesis. Moreover, constitutive inactivation of PRC1.1 results in unchecked expansion of GMPs and eventual transformation. Collectively, our results define PRC1.1 as a novel critical regulator of emergency myelopoiesis, dysregulation of which leads to myeloid transformation.

immunology↗