Open AccessZfp281 Functions as a Transcriptional Repressor for Pluripotency of Mouse Embryonic Stem Cells
Author(s) -
Fidalgo Miguel,
Shekar P. Chandra,
Ang YenSin,
Fujiwara Yuko,
Orkin Stuart H.,
Wang Jianlong
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.736
Subject(s) - homeobox protein nanog , biology , sox2 , rex1 , embryonic stem cell , nanog homeobox protein , embryoid body , microbiology and biotechnology , inner cell mass , transcription factor , stem cell , chromatin immunoprecipitation , cellular differentiation , genetics , induced pluripotent stem cell , promoter , gene expression , blastocyst , gene , embryogenesis , embryo
Embryonic stem cells (ESCs) derived from preimplantation blastocysts have unique self‐renewal and multilineage differentiation properties that are controlled by key components of a core regulatory network including Oct4, Sox2, and Nanog. Understanding molecular underpinnings of these properties requires identification and characterization of additional factors that act in conjunction with these key factors in ESCs. We have previously identified Zfp281, a Krüppel‐like zinc finger transcription factor, as an interaction partner of Nanog. We now present detailed functional analyses of Zfp281 using a genetically ablated null allele in mouse ESCs. Our data show that while Zfp281 is dispensable for establishment and maintenance of ESCs, it is required for their proper differentiation in vitro. We performed microarray profiling in combination with previously published datasets of Zfp281 global target gene occupancy and found that Zfp281 mainly functions as a repressor to restrict expression of many stem cell pluripotency genes. In particular, we demonstrated that deletion of Zfp281 resulted in upregulation of Nanog at both the transcript and protein levels with concomitant compromised differentiation of ESCs during embryoid body culture. Chromatin immunoprecipitation experiments demonstrated that Zfp281 is required for Nanog binding to its own promoter, suggesting that Nanog‐associated repressive complex(es) involving Zfp281 may fine‐tune Nanog expression for pluripotency of ESCs. S TEM C ELLS 2011;29:1705–1716