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

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Koh DI,Yoon JH,Kim MK,An H,Kim MY,Hur MW

doi

10.1016/j.bbrc.2013.11.046

subject

Has Abstract

pub_date

2013-12-13 00:00:00

pages

177-82

issue

3-4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(13)01928-1

journal_volume

442

pub_type

杂志文章

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