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Title: Kaiso is a key regulator of spleen germinal center formation by repressing Bcl6 expression in splenocytes

Abstract

Highlights: •Knockout of Kaiso results in concordant high expression of Bcl6 and c-Myc in spleen. •Kaiso binds the Bcl6 promoter and represses Bcl6 transcription by recruiting NCoR. •Upregulated Bcl6 increases splenocyte proliferation and causes large diffused GC. •Cell cycle-inhibition genes such as Cdkn1b and Cdkn1a are repressed by Bcl6. -- Abstract: Kaiso was previously described as a methylated DNA-binding protein and a transcription repressor interacting with the corepressor protein complex NCoR. In the current study, we show that generation-3 Kaiso knockout mice show a phenotype of splenomegaly and large diffused germinal centers (GC). In the spleens of Kaiso knockout mice, Bcl6 (a transcriptional repressor that plays a critical role in GC development in spleen) and c-Myc were highly expressed, while the cell cycle arrest genes p27 (CDKN1B), p21 (CDKN1A) and Gadd45a were downregulated. Chromatin immunoprecipitation (ChIP) and transcription assays suggested that Kaiso represses Bcl6 expression, and in Kaiso knockout mice, derepressed Bcl6 increased cell proliferation by suppressing p27 (CDKN1B), p21 (CDKN1A) and Gadd45a, while upregulating the oncogene c-Myc. Further evidence for Kaiso regulation of splenomegaly was provided by B lymphocyte Ramos cells, in which ectopic KAISO repressed BCL6 and c-MYC expression, while concomitantly increasing the expression of the cell cyclemore » arrestors p21, p27 and Gadd45a. In summary, derepressed Bcl6 expression may be responsible for increases in GC cell proliferation and splenomegaly of Kaiso knockout mice.« less

Authors:
; ; ; ; ;
Publication Date:
OSTI Identifier:
22242229
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 442; Journal Issue: 3-4; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL CYCLE; CELL PROLIFERATION; DNA; INHIBITION; KNOCK-OUT REACTIONS; LYMPHOCYTES; LYMPHOMAS; MICE; MONOCLINIC LATTICES; ONCOGENES; PHENOTYPE; PROTEINS; SPLEEN; SPLENOMEGALY; TRANSCRIPTION

Citation Formats

Koh, Dong-In, Yoon, Jae-Hyeon, Kim, Min-Kyeong, An, Haemin, Kim, Min-Young, and Hur, Man-Wook. Kaiso is a key regulator of spleen germinal center formation by repressing Bcl6 expression in splenocytes. United States: N. p., 2013. Web. doi:10.1016/J.BBRC.2013.11.046.
Koh, Dong-In, Yoon, Jae-Hyeon, Kim, Min-Kyeong, An, Haemin, Kim, Min-Young, & Hur, Man-Wook. Kaiso is a key regulator of spleen germinal center formation by repressing Bcl6 expression in splenocytes. United States. https://doi.org/10.1016/J.BBRC.2013.11.046
Koh, Dong-In, Yoon, Jae-Hyeon, Kim, Min-Kyeong, An, Haemin, Kim, Min-Young, and Hur, Man-Wook. 2013. "Kaiso is a key regulator of spleen germinal center formation by repressing Bcl6 expression in splenocytes". United States. https://doi.org/10.1016/J.BBRC.2013.11.046.
@article{osti_22242229,
title = {Kaiso is a key regulator of spleen germinal center formation by repressing Bcl6 expression in splenocytes},
author = {Koh, Dong-In and Yoon, Jae-Hyeon and Kim, Min-Kyeong and An, Haemin and Kim, Min-Young and Hur, Man-Wook},
abstractNote = {Highlights: •Knockout of Kaiso results in concordant high expression of Bcl6 and c-Myc in spleen. •Kaiso binds the Bcl6 promoter and represses Bcl6 transcription by recruiting NCoR. •Upregulated Bcl6 increases splenocyte proliferation and causes large diffused GC. •Cell cycle-inhibition genes such as Cdkn1b and Cdkn1a are repressed by Bcl6. -- Abstract: Kaiso was previously described as a methylated DNA-binding protein and a transcription repressor interacting with the corepressor protein complex NCoR. In the current study, we show that generation-3 Kaiso knockout mice show a phenotype of splenomegaly and large diffused germinal centers (GC). In the spleens of Kaiso knockout mice, Bcl6 (a transcriptional repressor that plays a critical role in GC development in spleen) and c-Myc were highly expressed, while the cell cycle arrest genes p27 (CDKN1B), p21 (CDKN1A) and Gadd45a were downregulated. Chromatin immunoprecipitation (ChIP) and transcription assays suggested that Kaiso represses Bcl6 expression, and in Kaiso knockout mice, derepressed Bcl6 increased cell proliferation by suppressing p27 (CDKN1B), p21 (CDKN1A) and Gadd45a, while upregulating the oncogene c-Myc. Further evidence for Kaiso regulation of splenomegaly was provided by B lymphocyte Ramos cells, in which ectopic KAISO repressed BCL6 and c-MYC expression, while concomitantly increasing the expression of the cell cycle arrestors p21, p27 and Gadd45a. In summary, derepressed Bcl6 expression may be responsible for increases in GC cell proliferation and splenomegaly of Kaiso knockout mice.},
doi = {10.1016/J.BBRC.2013.11.046},
url = {https://www.osti.gov/biblio/22242229}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3-4,
volume = 442,
place = {United States},
year = {Fri Dec 13 00:00:00 EST 2013},
month = {Fri Dec 13 00:00:00 EST 2013}
}