A5048051556- Retinoids in leukemia and cellular processes
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Acute Myeloid Leukemia Research
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- DNA Repair Mechanisms
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Endoplasmic Reticulum Stress and Disease
- FOXO transcription factor regulation
- Bone Metabolism and Diseases
- Signaling Pathways in Disease
- PARP inhibition in cancer therapy
- Cancer-related molecular mechanisms research
- Ferroptosis and cancer prognosis
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Chromatin Remodeling and Cancer
Fudan University Shanghai Cancer Center
2020-2025
State Key Laboratory of Genetic Engineering
2025
Tongji University
2024-2025
Shanghai Medical College of Fudan University
2020-2024
Shanghai Institute of Hematology
2018-2019
Shanghai Jiao Tong University
2018-2019
Ruijin Hospital
2018
Dephosphorylating RNA polymerase II Transcription in metazoans requires coordination of multiple factors to control the progression polymerases and integrity their products. Zheng et al. identified a new dual-enzyme complex called INTAC, which is composed protein phosphatase 2A (PP2A) core enzyme multisubunit endonuclease Integrator. Structural functional studies show that INTAC functions as noncanonical PP2A holoenzyme dephosphorylates C-terminal domain attenuate transcription. This study...
Abstract The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions 1,2 . Here we identify a stable association between the genome-stability regulator sensor single-stranded DNA (SOSS) 3 Integrator-PP2A (INTAC) 4–6 Through SSB1-mediated recognition DNA, SOSS–INTAC stimulates promoter-proximal termination attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced instability....
Transcription progression is governed by multitasking regulators including SPT5, an evolutionarily conserved factor implicated in virtually all transcriptional steps from enhancer activation to termination. Here we utilize a rapid degradation system and reveal crucial functions of SPT5 maintaining cellular chromatin RNA polymerase II (Pol II) levels. Rapid depletion causes pronounced reduction paused Pol at promoters enhancers, distinct negative elongation (NELF) resulting short-distance...
Estrogen receptor α (ERα) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcriptional events that promote tumor growth. ERα activity largely depends on access sites chromatin, which is facilitated part Pioneer Factors (PFs). Transcription factors operate complexes through thousands genomic a combinatorial fashion control expression genes. However, extent crosstalk cooperation between pioneer more collaborative transcription cancer...
Abstract The lung metastasis of breast cancer involves complicated regulatory changes driven by chromatin remodelling. However, the epigenetic reprogramming and mechanisms in remain unclear. Here, we generated analysed genome‐wide profiles multiple histone modifications (H3K4me3, H3K27ac, H3K27me3, H3K4me1 H3K9me3), as well transcriptome data lung‐metastatic non‐lung‐metastatic cells. Our results showed that expression were correlated with enrichment specific promoters enhancers. Promoter...
Abstract Background A hallmark of acute promyelocytic leukemia (APL) is the expression PML/RARα fusion protein. Treatment with all-trans retinoic acid (ATRA) results in terminal differentiation neutrophil granulocytes. However, underlying mechanisms remain largely unknown. Here, we identify and elucidate a novel differentiation-suppressive model APL involving histone demethylase KDM3B, which has been identified as suppressor tumor genes involved hematopoietic malignancies. Methods First,...
Abstract Integrator-PP2A (INTAC) is a highly modular complex orchestrating the transition of paused RNA polymerase II into productive elongation or promoter-proximal premature termination, with its loss resulting in transcription dysregulation and genome instability. Here, we identify human DSS1—a flexible 70-residue protein found multiple functionally diverse complexes including 26S proteasome—as an integral subunit INTAC backbone. Structural analysis DSS1–INTAC, both alone association...