Interleukin-9 receptor gene is transcriptionally regulated by nucleolin in T-cell lymphoma cells.

Abstract

Interleukin-9 (IL-9) is a multifunctional cytokine that not only has roles in immune and inflammatory responses but also is involved in growth-promoting and anti-apoptotic activities in multiple transformed cell lines, which suggests a potential role in tumorigenesis. Over-expression of the receptor of IL-9 (IL-9R) occurs in several types of human leukemias and in radiation-induced mouse T-cell lymphoma (TL). The molecular mechanism that regulates transcription of the IL-9R gene (Il9r) during leukemogenesis is, however, not well understood. Using a mouse TL cell line that has high expression of Il9r, we sought to dissect its promoter structure. Here we show that the active promoter for Il9r is located in the 5'-flanking AT-rich region. Chromatin immunoprecipitation showed the opening of chromatin structure of the promoter region coupled with nucleolin binding in vivo. Immunohistochemical analysis confirmed the increased localization of nucleolin in the nuclei of TL cells. These data indicate that increased expression of Il9r is associated with an increased binding of nucleolin, coupled with chromatin opening, to an AT-rich region in the 5'-flanking region of Il9r in TL cells.

• Authors: Yi Shang, Shizuko Kakinuma, Mayumi Nishimura, Yoshiro Kobayashi, Kisaburo Nagata, Yoshiya Shimada
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 51 Issue 8 Pg. 619-27 (Aug 2012) ISSN: 1098-2744 [Electronic] United States
• PMID: 21809393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc.

Chemical References

• DNA, Neoplasm
• Phosphoproteins
• RNA-Binding Proteins
• Receptors, Interleukin-9
• nucleolin

Topics

• 5' Flanking Region (genetics)
• AT Rich Sequence (genetics)
• Amino Acid Sequence
• Animals
• Base Sequence
• Blotting, Western
• Cell Nucleus (metabolism)
• Chromatin Immunoprecipitation
• DNA, Neoplasm (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Immunohistochemistry
• Lymphoma, T-Cell (genetics, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Molecular Sequence Data
• Phosphoproteins (genetics, metabolism)
• Promoter Regions, Genetic (genetics)
• Protein Binding
• RNA-Binding Proteins (genetics, metabolism)
• Receptors, Interleukin-9 (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured