Lianmei Tan

Duke University

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She Chen

National Institute of Biological Sciences, Beijing

Xin‐Jian He

National Institute of Biological Sciences, Beijing

Peter B. Alexander

Duke University

Christopher C. Pan

Duke University

Ergang Wang

Duke University

Kun Xiang

Duke University

Qi-Jing Li

Agency for Science, Technology and Research

Yaosi Liang

Duke University

Cui‐Jun Zhang

Chinese Academy of Agricultural Sciences

Liuyang Wang

Shenyang Pharmaceutical University

Cooperative Institutions

Duke University

Duke Medical Center

National Institute of Biological Sciences, Beijing

Duke University Hospital

Chinese Academy of Sciences

Shanghai Jiao Tong University

University of North Carolina at Chapel Hill

Nanjing Agricultural University

University of Chinese Academy of Sciences

Central South University

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Arabidopsis histone acetyltransferase complex coordinates cytoplasmic histone acetylation and nuclear chromatin accessibility

Science Advances (2024)

Chan‐Juan Wu Xin Xu Dan‐Yang Yuan Zhenzhen Liu Lianmei Tan

Conserved type B histone acetyltransferases are recognized for their role in acetylating newly synthesized histones in the cytoplasm of eukaryotes. However, their involvement in regulating chromatin within the nucleus remains unclear. Our study shows that the Arabidopsis thaliana type B histone acetyltransferase HAG2 interacts with the histone chaperones MSI2, MSI3, and NASP, as well as the histones H3 and H4, forming a complex in both the cytoplasm and the nucleus. Within this complex, HAG2 and MSI2/3 constitute a histone acetylation module essential for acetylating histone H4 in the cytoplasm. Furthermore, this module works together with NASP to regulate histone acetylation, chromatin accessibility, and gene transcription in the nucleus. This complex enhances chromatin accessibility near transcription start sites while reducing accessibility near transcription termination sites. Our findings reveal a distinct role for the Arabidopsis type B histone acetyltransferase in the nucleus, shedding light on the coordination between cytoplasmic histone acetylation and nuclear chromatin regulation in plants.

Histone acetyltransferase

SAP30

Histone code

10.1126/sciadv.adp1840

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The Arabidopsis acetylated histone-binding protein BRAT1 forms a complex with BRP1 and prevents transcriptional silencing

Nature Communications (2016)

Cui‐Jun Zhang Xiaomei Hou Lianmei Tan Chang‐Rong Shao Huanwei Huang

Abstract Transposable elements and other repetitive DNA sequences are usually subject to DNA methylation and transcriptional silencing. However, anti-silencing mechanisms that promote transcription in these regions are not well understood. Here, we describe an anti-silencing factor, Bromodomain and ATPase domain-containing protein 1 (BRAT1), which we identified by a genetic screen in Arabidopsis thaliana . BRAT1 interacts with an ATPase domain-containing protein, BRP1 (BRAT1 Partner 1), and both prevent transcriptional silencing at methylated genomic regions. Although BRAT1 mediates DNA demethylation at a small set of loci targeted by the 5-methylcytosine DNA glycosylase ROS1, the involvement of BRAT1 in anti-silencing is largely independent of DNA demethylation. We also demonstrate that the bromodomain of BRAT1 binds to acetylated histone, which may facilitate the prevention of transcriptional silencing. Thus, BRAT1 represents a potential link between histone acetylation and transcriptional anti-silencing at methylated genomic regions, which may be conserved in eukaryotes.

DNA demethylation

10.1038/ncomms11715

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Neoadjuvant anti-4-1BB confers protection against spontaneous metastasis through low-affinity intratumor CD8+ T cells in triple-negative breast cancer

bioRxiv (Cold Spring Harbor Laboratory) (2025)

Bryan Jian Wei Lim Mingyong Liu Liuyang Wang Sharleen Li Ying Kong Tao Yin

ABSTRACT Neoadjuvant immunotherapy seeks to harness the primary tumor as a source of relevant tumor antigens to enhance systemic anti-tumor immunity through improved immunological surveillance. Despite having revolutionized the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC), a significant portion of patients remain unresponsive and succumb to metastatic recurrence post-treatment. Here, we found that optimally scheduled neoadjuvant administration of anti-4-1BB monotherapy was able to counteract metastases and prolong survival following surgical resection. Phenotypic and transcriptional profiling revealed enhanced 4-1BB expression on tumor-infiltrating intermediate (T int ), relative to progenitor (T prog ) and terminally exhausted (T term ) T cells. Furthermore, T int was enriched in low-affinity T cells. Treatment with anti-4-1BB drove clonal expansion of T int , with reduced expression of tissue-retention marker CD103 in T prog . This was accompanied by increased TCR clonotype sharing between paired tumors and pre-metastatic lungs. Further interrogation of sorted intratumor T cells confirmed enhanced T cell egress into circulation following anti-4-1BB treatment. In addition, gene signature extracted from anti-4-1BB treated T int was consistently associated with improved clinical outcomes in BRCA patients. Combinatorial neoadjuvant anti-4-1BB and ablation of tumor-derived CXCL16 resulted in enhanced therapeutic effect. These findings illustrate the intratumor changes underpinning the efficacy of neoadjuvant anti-4-1BB, highlighting the reciprocity between local tissue-retention and distant immunologic fortification, suggesting treatment can reverse the siphoning of intratumor T cells to primary tumor, enabling redistribution to distant tissues and subsequent protection against metastases.

Triple-negative breast cancer

Circulating tumor cell

Primary tumor

10.1101/2025.01.29.635356

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Amyloid-β precursor protein promotes tumor growth by establishing an immune-exclusive tumor microenvironment

bioRxiv (Cold Spring Harbor Laboratory) (2025)

Tao Yin Guoping Wang Zhehao Ma Liuyang Wang Rui Chen

During initiation and progression, cancerous tissue hijacks a series of elaborate tissue homeostatic mechanisms to avoid immune surveillance, including neuro-immune interactions. Here, we show that amyloid-β precursor protein (APP) and its β-cleavage product amyloid-β1-42 (Aβ1-42), well-known in the pathogenesis of Alzheimer′s disease (AD), are expressed in multiple cancer tissues. However, the oncogenic activity of APP is due to its E1 domain, instead of Aβ1-42. Mechanistically, APP restricts immune cells influx into tumor microenvironment (TME) and impairs CD8+ T cell and NK cell-based immunity, by dampening type I interferon (IFN) response in TME. We also provide proof-of-concept that vaccination targeting APP is effective for cancer prevention. Our current study reveals a previously unrecognized role of APP in cancer immune surveillance, and provides a new strategy for cancer prevention and treatment by targeting APP.

10.1101/2025.02.10.637339

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FHA2 is a plant‐specific ISWI subunit responsible for stamen development and plant fertility

Journal of Integrative Plant Biology (2020)

Bowen Gu Lianmei Tan Cui‐Jun Zhang Xiaomei Hou Xue‐Wei Cai

Abstract Imitation Switch (ISWI) chromatin remodelers are known to function in diverse multi‐subunit complexes in yeast and animals. However, the constitution and function of ISWI complexes in Arabidopsis thaliana remain unclear. In this study, we identified forkhead‐associated domain 2 (FHA2) as a plant‐specific subunit of an ISWI chromatin‐remodeling complex in Arabidopsis . By in vivo and in vitro analyses, we demonstrated that FHA2 directly binds to RLT1 and RLT2, two redundant subunits of the ISWI complex in Arabidopsis . The stamen filament is shorter in the fha2 and rlt1/2 mutants than in the wild type, whereas their pistil lengths are comparable. The shorter filament, which is due to reduced cell size, results in insufficient pollination and reduced fertility. The rlt1/2 mutant shows an early‐flowering phenotype, whereas the phenotype is not shared by the fha2 mutant. Consistent with the functional specificity of FHA2, our RNA‐seq analysis indicated that the fha2 mutant affects a subset of RLT1/2‐regulated genes that does not include genes involved in the regulation of flowering time. This study demonstrates that FHA2 functions as a previously uncharacterized subunit of the Arabidopsis ISWI complex and is exclusively involved in regulating stamen development and plant fertility.

10.1111/jipb.12945

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A plant‐specific SWR1 chromatin‐remodeling complex couples histone H2A.Z deposition with nucleosome sliding

The EMBO Journal (2020)

Yuxi Luo Xiaomei Hou Cui‐Jun Zhang Lianmei Tan Chang‐Rong Shao

Biological sciences

10.15252/embj.2019102008

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Citations (73)

Cancer-cell-derived GABA promotes β-catenin-mediated tumour growth and immunosuppression

Nature Cell Biology (2022)