A mouse-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for development

Modzelewski, A; Shao, Wanqing; Chen, Jingqi; Lee, Angus; Qi, Xin; Noon, Mackenzie; Tjokro, Kristy; Sales, Gabriele; Biton, Anne; Anand, Aparna; Speed, Terence P.; Xuan, Zhenyu; Wang, Ting; Risso, Davide; He, Lin

doi:10.1016/j.cell.2021.09.021

Cited by 65 publications

(55 citation statements)

References 110 publications

(70 reference statements)

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“…To address this issue, we used a transcript assembly approach that we recently developed ( Modzelewski et al 2021 ; Shao and Wang 2021 ). Briefly, we performed transcript assembly using all mapped RNA-seq reads and excluded all annotated protein-coding transcripts.…”

Section: Resultsmentioning

confidence: 99%

“…To investigate TEs’ contribution to tissue-specific alternative promoters, we identified novel TE-derived promoters. We used an approach similar to that previously used for the identification of TE onco-exaptation and TE-derived alternative promoters ( Jang et al 2019 ; Modzelewski et al 2021 ). In brief, we used all assembled transcripts from the 11 adult tissues and identified 7511 transcripts whose 5′ ends are mapped to TEs ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The MIRb element located in the intronic region of the ACE2 gene serves as an alternative promoter and generates a novel short ACE2 isoform in the airway epithelium, the main site of SARS-CoV-2 infection ( Ng et al 2020 ; Blume et al 2021 ). In mammalian preimplantation embryos, species-specific TEs serve as alternative promoters to generate truncated Cdk2ap1 isoforms, suggesting that TE-derived alternative promoters can yield evolutionarily conserved alternative protein isoforms ( Modzelewski et al 2021 ). However, similar TE promoter usage in zebrafish had not been reported.…”

Section: Discussionmentioning

confidence: 99%

“…TEs can also act as tissue-specific enhancers ( Xie et al 2013 ; Todd et al 2019 ) and chromatin boundaries ( Schmidt et al 2012 ; Choudhary et al 2020 ). Further, TEs have been found to provide transcription start sites and exons to both protein-coding genes and noncoding RNAs, affecting variation in transcription in both normal and disease states ( Kapusta et al 2013 ; Thompson et al 2016 ; Chishima et al 2018 ; Jang et al 2019 ; Pasquesi et al 2020 ; Modzelewski et al 2021 ).…”

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confidence: 99%

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Epigenomic analysis reveals prevalent contribution of transposable elements to cis-regulatory elements, tissue-specific expression, and alternative promoters in zebrafish

et al. 2022

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Transposable elements (TEs) encode regulatory elements that impact gene expression in multiple species, yet a comprehensive analysis of zebrafish TEs in the context of gene regulation is lacking. Here, we systematically investigate the epigenomic and transcriptomic landscape of TEs across eleven adult zebrafish tissues using multidimensional sequencing data. We find that TEs contribute substantially to a diverse array of regulatory elements in the zebrafish genome and that 37% of TEs are positioned in active regulatory states in adult zebrafish tissues. We identify TE subfamilies enriched in highly specific regulatory elements among different tissues. We use transcript assembly to discover TE-derived transcriptional units expressed across tissues. Finally, we show that novel TE-derived promoters can initiate tissue-specific transcription of alternate gene isoforms. This work provides a comprehensive profile of TE activity across normal zebrafish tissues, shedding light on mechanisms underlying the regulation of gene expression in this widely used model organism.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Epigenomic analysis reveals prevalent contribution of transposable elements to cis-regulatory elements, tissue-specific expression, and alternative promoters in zebrafish

et al. 2022

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“…LTRs are involved in many pathological processes, such as neurodegenerative diseases ( 7–9 ), cancer progression ( 10 , 11 ) and inflammatory bowel disease ( 12 ). In addition, LTRs are also involved in normal biological processes, illustrated by the recent report that species-specific LTRs shape its specific early embryonic development process and are essential for embryonic development ( 13 ). A few studies have shown that LTRs can enrich certain active histone modifications and transcription factors, and act as cis -regulatory elements to regulate host gene expression, such as serving as species-specific transcriptional insulators or providing transcription factor binding sites ( 14–16 ).…”

Section: Introductionmentioning

confidence: 99%

Active endogenous retroviral elements in human pluripotent stem cells play a role in regulating host gene expression

Zhang

Zheng

et al. 2022

Nucleic Acids Research

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Human endogenous retroviruses, also called LTR elements, can be bound by transcription factors and marked by different histone modifications in different biological contexts. Recently, individual LTR or certain subclasses of LTRs such as LTR7/HERVH and LTR5_Hs/HERVK families have been identified as cis-regulatory elements. However, there are still many LTR elements with unknown functions. Here, we dissected the landscape of histone modifications and regulatory map of LTRs by integrating 98 ChIP-seq data in human embryonic stem cells (ESCs), and annotated the active LTRs enriching enhancer/promoter-related histone marks. Notably, we found that MER57E3 functionally acted as proximal regulatory element to activate respective ZNF gene. Additionally, HERVK transcript could mainly function in nucleus to activate the adjacent genes. Since LTR5_Hs/LTR5 was bound by many early embryo-specific transcription factors, we further investigated the expression dynamics in different pluripotent states. LTR5_Hs/LTR5/HERVK exhibited higher expression level in naïve ESCs and extended pluripotent stem cells (EPSCs). Functionally, the LTR5_Hs/LTR5 with high activity could serve as a distal enhancer to regulate the host genes. Ultimately, our study not only provides a comprehensive regulatory map of LTRs in human ESCs, but also explores the regulatory models of MER57E3 and LTR5_Hs/LTR5 in host genome.

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Pivotal role for long noncoding RNAs in zygotic genome activation in mice

Chen,

Liu,

Zhu

et al. 2024

Sci. China Life Sci.

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A mouse-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for development

Cited by 65 publications

References 110 publications

Epigenomic analysis reveals prevalent contribution of transposable elements to cis-regulatory elements, tissue-specific expression, and alternative promoters in zebrafish

Epigenomic analysis reveals prevalent contribution of transposable elements to cis-regulatory elements, tissue-specific expression, and alternative promoters in zebrafish

Active endogenous retroviral elements in human pluripotent stem cells play a role in regulating host gene expression

Pivotal role for long noncoding RNAs in zygotic genome activation in mice

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