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Inducible expression of immediate early genes is regulated through dynamic chromatin association by NF45/ILF2 and NF90/NF110/ILF3.

ABSTRACT: Immediate early gene (IEG) transcription is rapidly activated by diverse stimuli. This transcriptional regulation is assumed to involve constitutively expressed nuclear factors that are targets of signaling cascades initiated at the cell membrane. NF45 (encoded by ILF2) and its heterodimeric partner NF90/NF110 (encoded by ILF3) are chromatin-interacting proteins that are constitutively expressed and localized predominantly in the nucleus. Previously, NF90/NF110 chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) in K562 erythroleukemia cells revealed its enriched association with chromatin at active promoters and strong enhancers. NF90/NF110 specifically occupied the promoters of IEGs. Here, ChIP in serum-starved HEK293 cells demonstrated that NF45 and NF90/NF110 pre-exist and specifically occupy the promoters of IEG transcription factors EGR1, FOS and JUN. Cellular stimulation with phorbol myristyl acetate increased NF90/NF110 chromatin association, while decreasing NF45 chromatin association at promoters of EGR1, FOS and JUN. In HEK293 cells stably transfected with doxycycline-inducible shRNA vectors targeting NF90/NF110 or NF45, doxycycline-mediated knockdown of NF90/NF110 or NF45 attenuated the inducible expression of EGR1, FOS, and JUN at the levels of transcription, RNA and protein. Dynamic chromatin association of NF45 and NF90/NF110 at IEG promoters are observed upon stimulation, and NF45 and NF90/NF110 contribute to inducible transcription of IEGs. NF45 and NF90/NF110 operate as chromatin regulators of the immediate early response.

SUBMITTER: Wu TH

PROVIDER: S-EPMC6483252 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Inducible expression of immediate early genes is regulated through dynamic chromatin association by NF45/ILF2 and NF90/NF110/ILF3.

Wu Ting-Hsuan TH Shi Lingfang L Lowe Anson W AW Nicolls Mark R MR Kao Peter N PN

PloS one 20190425 4

Immediate early gene (IEG) transcription is rapidly activated by diverse stimuli. This transcriptional regulation is assumed to involve constitutively expressed nuclear factors that are targets of signaling cascades initiated at the cell membrane. NF45 (encoded by ILF2) and its heterodimeric partner NF90/NF110 (encoded by ILF3) are chromatin-interacting proteins that are constitutively expressed and localized predominantly in the nucleus. Previously, NF90/NF110 chromatin immunoprecipitation foll ...[more]

PMID: 31022259

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Project description:Esophageal cancer (EC) is a common malignant disease in eastern countries. However, a study of the metabolomic characteristics associated with other biological factors in esophageal squamous cell carcinoma (ESCC) is limited. Interleukin enhancer binding factor 2 (ILF2) and ILF3, double-stranded RNA-binding proteins, have been reported to contribute to the occurrence and development of various types of malignancy. Nevertheless, the underlying functions of ILF2 and ILF3 in ESCC metabolic reprogramming have never been reported. This study aimed to contribute to the metabolic characterization of ESCC and to investigate the metabolomic alterations associated with ILF2 and ILF3 in ESCC tissues. Here, we identified 112 differential metabolites, which were mainly enriched in phosphatidylcholine biosynthesis, fatty acid metabolism, and amino acid metabolism pathways, based on liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry approaches using ESCC tissues and paired para-cancer tissues from twenty-eight ESCC patients. In addition, ILF2 and ILF3 expression were significantly elevated in EC tissues compared to the histologically normal samples, and closely associated with PI3K/AKT and MAPK signaling pathways in ESCC. Moreover, in ESCC tissues with a high ILF2 expression, several short-chain acyl-carnitines (C3:0, C4:0, and C5:0) related to the BCAA metabolic pathway and long-chain acyl-carnitines (C14:0, C16:0, C16:0-OH, and C18:0) involved in the oxidation of fatty acids were obviously upregulated. Additionally, a series of intermediate metabolites involved in the glycolysis pathway, including G6P/F6P, F1,6BP, DHAP, G3P, and 2,3BPG, were remarkably downregulated in highly ILF3-expressed ESCC tissues compared with the corresponding para-cancer tissues. Overall, these findings may provide evidence for the roles of ILF2 and ILF3 during the process of ESCC metabolic alterations, and new insights into the development of early diagnosis and treatment for ESCC. Further investigation is needed to clarify the underlying mechanism of ILF2 and ILF3 on acyl-carnitines and the glycolysis pathway, respectively.

Dataset Information

Inducible expression of immediate early genes is regulated through dynamic chromatin association by NF45/ILF2 and NF90/NF110/ILF3.

Publications

Inducible expression of immediate early genes is regulated through dynamic chromatin association by NF45/ILF2 and NF90/NF110/ILF3.

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