title: 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.
authors.affiliation: Brain Korea 21 Plus Project for Medical Sciences, Department of Biochemistry and Molecular Biology, Severance Biomedical Research Institute, Yonsei University School of Medicine, 134 ShinChon-Dong, SeoDaeMoon-Ku, Seoul 120-752, Republic of Korea.
authors.forename: Dong-In
authors.initials: DI
authors.lastname: Koh
authors.forename: Jae-Hyeon
authors.initials: JH
authors.lastname: Yoon
authors.forename: Min-Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Haemin
authors.initials: H
authors.lastname: An
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Man-Wook
authors.initials: MW
authors.lastname: Hur
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism; D009929:Organ Size; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000473:pathology*; D013163:Splenomegaly / Q000235:genetics / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C539128:Ncor1 protein, mouse; D056971:Nuclear Receptor Co-Repressor 1; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D014157:Transcription Factors; C118822:Zbtb33 protein, mouse
keywords: B cell; B-cell lymphoma 6 protein; BCL6; Bcl6; Cell proliferation; DLBCL; Diffuse large B-cell lymphoma; GC; Germinal center; Kaiso; Spleen; Splenomegaly; germinal center