title: Patz1 regulates embryonic stem cell identity.
abstract: Embryonic stem cells (ESCs) derived from the inner cell mass (ICM) of blastocysts are pluripotent. Pluripotency is maintained by a transcriptional network in which Oct4 and Nanog are master regulators. Notably, several zinc finger transcription factors have important roles in this network. Patz1, a BTB/POZ-domain-containing zinc finger protein, is expressed at higher levels in the ICM relative to the trophectoderm. However, its function in pluripotency has been poorly studied. Here, we show that Patz1 is an important regulator of pluripotency in ESCs. Patz1 RNAi, chromatin immunoprecipitation (ChIP), and reporter assays indicate that Patz1 directly regulates Pou5f1 and Nanog. Global transcriptome changes upon Patz1 knockdown largely involve upregulation of apoptotic genes and downregulation of cell cycle and cellular metabolism genes. Patz1 ChIP sequencing further identified more than 5,000 binding sites of Patz1 in mouse genome, from which two binding motifs were extracted. Further, gene ontology analysis of genes associated with the binding sites displays enrichment for proximity to developmental genes. In addition, embryoid body assays suggest that Patz1 represses developmental genes. Together, these results propose that Patz1 is important for ESC pluripotency.
authors.affiliation: 1 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore , Singapore, Singapore .
authors.forename: Jin Rong
authors.initials: JR
authors.lastname: Ow
authors.forename: Hui
authors.initials: H
authors.lastname: Ma
authors.forename: Angela
authors.initials: A
authors.lastname: Jean
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Goh
authors.forename: Yun Hwa
authors.initials: YH
authors.lastname: Lee
authors.forename: Yew Mei
authors.initials: YM
authors.lastname: Chong
authors.forename: Richie
authors.initials: R
authors.lastname: Soong
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Fu
authors.forename: Henry
authors.initials: H
authors.lastname: Yang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000818:Animals; D002460:Cell Line; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis; D051379:Mice; D000071317:Nanog Homeobox Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012097:Repressor Proteins; C485875:Zfp278 protein, mouse