title: ZBTB32 is an early repressor of the CIITA and MHC class II gene expression during B cell differentiation to plasma cells.
abstract: CIITA and MHC class II expression is silenced during the differentiation of B cells to plasma cells. When B cell differentiation is carried out ex vivo, CIITA silencing occurs rapidly, but the factors contributing to this event are not known. ZBTB32, also known as repressor of GATA3, was identified as an early repressor of CIITA in an ex vivo plasma cell differentiation model. ZBTB32 activity occurred at a time when B lymphocyte-induced maturation protein-1 (Blimp-1), the regulator of plasma cell fate and suppressor of CIITA, was minimally induced. Ectopic expression of ZBTB32 suppressed CIITA and I-A gene expression in B cells. Short hairpin RNA depletion of ZBTB32 in a plasma cell line resulted in re-expression of CIITA and I-A. Compared with conditional Blimp-1 knockout and wild-type B cells, B cells from ZBTB32/ROG-knockout mice displayed delayed kinetics in silencing CIITA during ex vivo plasma cell differentiation. ZBTB32 was found to bind to the CIITA gene, suggesting that ZBTB32 directly regulates CIITA. Lastly, ZBTB32 and Blimp-1 coimmunoprecipitated, suggesting that the two repressors may ultimately function together to silence CIITA expression. These results introduce ZBTB32 as a novel regulator of MHC-II gene expression and a potential regulatory partner of Blimp-1 in repressing gene expression.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Yoon
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Scharer
authors.forename: Parimal
authors.initials: P
authors.lastname: Majumder
authors.forename: Carl W
authors.initials: CW
authors.lastname: Davis
authors.forename: Royce
authors.initials: R
authors.lastname: Butler
authors.forename: Wendy
authors.initials: W
authors.lastname: Zinzow-Kramer
authors.forename: Ioanna
authors.initials: I
authors.lastname: Skountzou
authors.forename: Dimitrios G
authors.initials: DG
authors.lastname: Koutsonanos
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Boss
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D020868:Gene Silencing / Q000276:immunology*; D057809:HEK293 Cells; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012097:Repressor Proteins; C406863:Rog protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors