Lin28A Binds Active Promoters and Recruits Tet1 to Regulate Gene Expression

Zeng, Yue; Yao, Bing; Shin, Jaehoon; Lin, Li; Kim, Namshik; Song, Qifeng; Liu, Shuang; Su, Yijing; Guo, Junjie U.; Huang, Luoxiu; Wan, Jun; Wu, Hao; Qian, Jiang; Cheng, Xiaodong; Zhu, Heng; Ming, Guo Li; Jin, Peng; Song, Hongjun

doi:10.1016/j.molcel.2015.11.020

Cited by 85 publications

(68 citation statements)

References 38 publications

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“…Although LIN28B is documented to inhibit miRNA maturation, the present study showed that LIN28B knockdown reduced the expression of several C19MC miRNAs. These unexpected results may be explained by a recent study demonstrating that LIN28 binds directly to a consensus DNA sequence at promoter regions and recruits the CpG demethylase TET1 to activate transcription (58). Moreover, analysis of published PAR-CLIP results indicate that LIN28B can bind to CpG rich-Alu repeats dispersed throughout C19MC (29) that can function as independent promoters for RNA polymerase III and transcriptionally activate C19MC (59)(60)(61).…”

Section: Discussionmentioning

confidence: 99%

Decreased LIN28B in preeclampsia impairs human trophoblast differentiation and migration

Canfield¹,

Arlıer²,

Mong³

et al. 2018

FASEB j.

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Preeclampsia (PE) is a common cause of maternal morbidity, characterized by impaired trophoblast invasion and spiral artery transformation resulting in progressive uteroplacental hypoxia. Given the primary role of LIN28A and LIN28B in modulating cell metabolism, differentiation, and invasion, we hypothesized that LIN28A and/or LIN28B regulates trophoblast differentiation and invasion, and that its dysregulation may contribute to PE. Here we show that LIN28B is expressed ∼1300‐fold higher than LIN28A in human term placenta and is the predominant paralog expressed in primary human trophoblast cultures. The expression of LIN28B mRNA and protein levels are significantly reduced in gestational age–matched preeclamptic vs. normal placentas, whereas LIN28A expression is not different. First trimester human placental sections displayed stronger LIN28B immunoreactivity in extravillous (invasive) cytotrophoblasts and syncytial sprouts vs. villous trophoblasts. LIN28B overexpression increased HTR8 cell proliferation, migration, and invasion, whereas LIN28B knockdown in JEG3 cells reduced cell proliferation. Moreover, LIN28B knockdown in JEG3 cells suppressed syncytin 1 (SYN‐1), apelin receptor early endogenous ligand (ELABELA), and the chromosome 19 microRNA cluster, and increased mRNA expression of ITGp4and TNF‐α. Incubation of BeWo and JEG3 cells under hypoxia significantly decreased expression of LIN28B and LIN28A, SYN‐1, and ELABELA, whereas TNF‐α is increased. These results provide the first evidence that LIN28B is the predominant paralog in human placenta and that decreased LIN28B may play a role in PE by reducing trophoblast invasion and syncytialization, and by promoting inflammation.—Canfield, J., Arlier, S., Mong, E. F., Lockhart, J., Vanwye, J., Guzeloglu‐Kayisli, O., Schatz, F., Magness, R. R., Lockwood, C. J., Tsibris, J. C. M., Kayisli, U. A., Totary‐Jain, H. Decreased LIN28B in preeclampsia impairs human trophoblast differentiation and migration. FASEB J. 33, 2759–2769 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Decreased LIN28B in preeclampsia impairs human trophoblast differentiation and migration

Canfield¹,

Arlıer²,

Mong³

et al. 2018

FASEB j.

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“…As an important epigenetic modification enzyme, Tet1 interact with other proteins by forming protein complex58, transcription factor Lin28 regulate gene expression through recruitment of TET159. An active DNA demethylation process occurs with an involvement of TET enzymes, and the expression level of TET1–3 is critical for human spermiogenesis and male fertility31.…”

Section: Discussionmentioning

confidence: 99%

The Modification of Tet1 in Male Germline Stem Cells and Interact with PCNA, HDAC1 to promote their Self-renewal and Proliferation

Zheng

Zhai

et al. 2016

Sci Rep

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Epigenetic modification plays key roles in spermatogenesis, especially DNA methylation dynamic is important in sustaining normal spermatogenesis. Ten-eleven translocation 1 (Tet1) is not only a key demethylase, which works in specific gene regions, but also crosstalks with partners to regulate epigenetic progress as protein complexes. Dairy goat is an important livestock in China, while the unstable culture system in vitro inhibits optimization of new dairy goat species. The study of epigenetic modification in male germline stem cells (mGSCs) is beneficial to the optimization of adult stem cell culture system in vitro, and the improvement of sperm quality and breeding of selected livestock. In our study, we not only analyzed the morphology, gene expression, DNA methylation and histone methylation dynamic in mouse Tet1 (mTet1) modified mGSCs, we also analyzed the stemness ability by in vivo transplantation and explored the functional mechanism of Tet1 in dairy goat mGSCs. The results showed mTet1 modified mGSCs had better self-renewal and proliferation ability than wild-type mGSCs, mTet1 could also up-regulate JMJD3 to decrease H3K27me3, which also showed to suppress the MEK-ERK pathway. Furthermore, Co-IP analysis demonstrated that TET1 interact with PCNA and HDAC1 by forming protein complexes to comprehensively regulate dairy goat mGSCs and spermatogenesis.

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“…In mouse ESCs, LIN28A could recruit and form a complex with TET1 to promote 5mC‐to‐5hmC conversion and demethylation at 5′ upstream region of genes (Zeng et al, ). When we treated GmGSCs‐I‐SB cell line with 2 μM 5‐azacytidine (an inhibitor of DNA methylation), the NANOG expression was upregulated significantly (Figure a), which indicated that DNA demethylation was probably involved in the activation of NANOG transcription.…”

Section: Resultsmentioning

confidence: 99%

LIN28A activates the transcription of NANOG in dairy goat male germline stem cells

Wei

et al. 2018

Journal Cellular Physiology

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LIN28A serves as a crucial marker of dairy goat male germline stem cells (GmGSCs). In our previous study, we demonstrated that LIN28A promotes proliferation, self‐renewal, and maintains the stemness of GmGSCs. Here, we found that LIN28A could activate the transcription of NANOG in a let‐7g independent manner. We cloned the 5′ upstream of two NANOG genes which were located on chromosome 15 ( NANOG‐ch15) and chromosome 5 ( NANOG‐ch5), respectively, and then examined their promoter activities and promoter methylation levels. Results showed that NANOG‐ch15 is a pseudogene whereas NANOG‐ch5 is active in Capra hircus. Bioinformatics analysis indicated that the 5′ upstream region of NANOG‐ch5 does not have typical CpG islands but contains several CG enrichment regions and several LIN28A binding sites. Deletion analysis suggested that NANOG‐ch5 promoter can be activated by LIN28A directly binding to the site ‐210 but not by the indirect effect from the inhibition of let‐7g, which is known to be downregulated by LIN28A. Mechanistically, LIN28A recruits and interacts with 5‐methylcytosine‐dioxygenase Ten‐Eleven translocation 1 (TET1) to NANOG‐ch5 gene promoter binding sites to orchestrate 5‐methylcytosine and 5‐hydroxymethylcytosine dynamics. These results revealed the role of LIN28A in NANOG transcriptional regulation via epigenetic DNA modifications to maintain the stemness of GmGSC.

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Lin28A Binds Active Promoters and Recruits Tet1 to Regulate Gene Expression

Cited by 85 publications

References 38 publications

Decreased LIN28B in preeclampsia impairs human trophoblast differentiation and migration

Decreased LIN28B in preeclampsia impairs human trophoblast differentiation and migration

The Modification of Tet1 in Male Germline Stem Cells and Interact with PCNA, HDAC1 to promote their Self-renewal and Proliferation

LIN28A activates the transcription of NANOG in dairy goat male germline stem cells

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