title: Critical POU domain residues confer Oct4 uniqueness in somatic cell reprogramming.
abstract: The POU domain transcription factor Oct4 plays critical roles in self-renewal and pluripotency of embryonic stem cells (ESCs). Together with Sox2, Klf4 and c-Myc, Oct4 can reprogram any other cell types to pluripotency, in which Oct4 is the only factor that cannot be functionally replaced by other POU family members. To investigate the determinant elements of Oct4 uniqueness, we performed Ala scan on all Ser, Thr, Tyr, Lys and Arg of murine Oct4 by testing their capability in somatic cell reprogramming. We uncovered a series of residues that are important for Oct4 functionality, in which almost all of these key residues are within the POU domains making direct interaction with DNA. The Oct4 N- and C-terminal transactivation domains (TADs) are not unique and could be replaced by the Yes-associated protein (YAP) TAD domain to support reprogramming. More importantly, we uncovered two important residues that confer Oct4 uniqueness in somatic cell reprogramming. Our systematic structure-function analyses bring novel mechanistic insight into the molecular basis of how critical residues function together to confer Oct4 uniqueness among POU family for somatic cell reprogramming.
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang, Beijing 100101, P.R.China.|State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang, Beijing 100101, P.R.China.
authors.forename: Wensong
authors.initials: W
authors.lastname: Jin
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, P.R.China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang, Beijing 100101, P.R.China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang, Beijing 100101, P.R.China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang, Beijing 100101, P.R.China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang, Beijing 100101, P.R.China.
authors.forename: Dahua
authors.initials: D
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang, Beijing 100101, P.R.China.
authors.forename: Qinmiao
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, P.R.China.
authors.forename: Zongping
authors.initials: Z
authors.lastname: Xia
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002454:Cell Differentiation; D065150:Cellular Reprogramming / Q000235:genetics*; D018360:Crystallography, X-Ray; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D000071317:Nanog Homeobox Protein / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D061251:Primary Cell Culture; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014162:Transfection
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489427:MYC protein, human; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse