title: GATA family members as inducers for cellular reprogramming to pluripotency.
abstract: Members of the GATA protein family play important roles in lineage specification and transdifferentiation. Previous reports show that some members of the GATA protein family can also induce pluripotency in somatic cells by substituting for Oct4, a key pluripotency-associated factor. However, the mechanism linking lineage-specifying cues and the activation of pluripotency remains elusive. Here, we report that all GATA family members can substitute for Oct4 to induce pluripotency. We found that all members of the GATA family could inhibit the overrepresented ectodermal-lineage genes, which is consistent with previous reports indicating that a balance of different lineage-specifying forces is important for the restoration of pluripotency. A conserved zinc-finger DNA-binding domain in the C-terminus is critical for the GATA family to induce pluripotency. Using RNA-seq and ChIP-seq, we determined that the pluripotency-related gene Sall4 is a direct target of GATA family members during reprogramming and serves as a bridge linking the lineage-specifying GATA family to the pluripotency circuit. Thus, the GATA family is the first protein family of which all members can function as inducers of the reprogramming process and can substitute for Oct4. Our results suggest that the role of GATA family in reprogramming has been underestimated and that the GATA family may serve as an important mediator of cell fate conversion.
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Shu
authors.affiliation: 1] The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China [2] Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: 1] Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Zhang
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Anzhi
authors.initials: A
authors.lastname: Yao
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Sida
authors.initials: S
authors.lastname: Shao
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Du
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Yang
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Chen
authors.affiliation: The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.affiliation: Beijing Vitalstar Biotechnology Co., Ltd., Beijing 100012, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yang
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 1] The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China [2] Shenzhen Stem Cell Engineering Laboratory, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, China [3] Peking University Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Hongkui
authors.initials: H
authors.lastname: Deng
mesh_terms: D000818:Animals; D002460:Cell Line; D019070:Cell Lineage; D065150:Cellular Reprogramming; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D050980:GATA Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D011485:Protein Binding; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; C088334:Distal-less homeobox proteins; D050980:GATA Transcription Factors; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C102995:Lhx5 protein, mouse; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D009419:Nerve Tissue Proteins; D050814:Octamer Transcription Factor-3; C509167:Sall4 protein, mouse; D014157:Transcription Factors; D004247:DNA