GATA family members as inducers for cellular reprogramming to pluripotency

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 mec...

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Bibliographic Details
Published in:Cell research 2015-02, Vol.25 (2), p.169-180
Main Authors: Shu, Jian, Zhang, Ke, Zhang, Minjie, Yao, Anzhi, Shao, Sida, Du, Fengxia, Yang, Caiyun, Chen, Wenhan, Wu, Chen, Yang, Weifeng, Sun, Yingli, Deng, Hongkui
Format: Article
Language:English
Subjects:
Animals
Cell Line
Cell Lineage
Cellular Reprogramming
DNA - chemistry
DNA - metabolism
DNA-Binding Proteins - metabolism
DNA结合结构域
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
GATA Transcription Factors - chemistry
GATA Transcription Factors - genetics
GATA Transcription Factors - metabolism
HEK293 Cells
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - metabolism
LIM-Homeodomain Proteins - genetics
LIM-Homeodomain Proteins - metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutagenesis, Site-Directed
Nanog Homeobox Protein
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Octamer Transcription Factor-3 - metabolism
Original
Protein Binding
Sequence Analysis, RNA
Transcription Factors - genetics
Transcription Factors - metabolism
Zinc Fingers
体细胞
多能性
家庭成员
相关基因
编程过程
诱导剂
重新编程
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Summary: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 ChlP-seq, we determined that the pluripotency-related gene Sail4 is a direct target of GATA family members during reprogramming and serves as a bridge linking the lineage-specifying GATA family to the plnripotency 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.
ISSN:1001-0602
1748-7838
DOI:10.1038/cr.2015.6