lincRNAs in Vertebrate Development

Team Publications

Year of publication 2018

Bitetti A, Mallory AC, Carrieri C, Golini E, Carreño Gutierrez H, Perlas E, Pérez-Rico YA, Tocchini-Valentini GP, Enright AJ, Norton WHJ, Mandillo S, O’Carroll D, Shkumatava A (in press) (2018 Feb 21)

MicroRNA degradation by a conserved target RNA regulates animal behavior

Nat Struct .Mol Biol Learn more

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Year of publication 2017

Matthew P Davis, Claudia Carrieri, Harpreet K Saini, Stijn van Dongen, Tommaso Leonardi, Giovanni Bussotti, Jack M Monahan, Tania Auchynnikava, Angelo Bitetti, Juri Rappsilber, Robin C Allshire, Alena Shkumatava, Dónal O'Carroll, Anton J Enright (2017 May 14)

Transposon-driven transcription is a conserved feature of vertebrate spermatogenesis and transcript evolution.

EMBO reports : 1231-1247 : DOI : 10.15252/embr.201744059 Learn more

Spermatogenesis is associated with major and unique changes to chromosomes and chromatin. Here, we sought to understand the impact of these changes on spermatogenic transcriptomes. We show that long terminal repeats (LTRs) of specific mouse endogenous retroviruses (ERVs) drive the expression of many long non-coding transcripts (lncRNA). This process occurs post-mitotically predominantly in spermatocytes and round spermatids. We demonstrate that this transposon-driven lncRNA expression is a conserved feature of vertebrate spermatogenesis. We propose that transposon promoters are a mechanism by which the genome can explore novel transcriptional substrates, increasing evolutionary plasticity and allowing for the genesis of novel coding and non-coding genes. Accordingly, we show that a small fraction of these novel ERV-driven transcripts encode short open reading frames that produce detectable peptides. Finally, we find that distinct ERV elements from the same subfamilies act as differentially activated promoters in a tissue-specific context. In summary, we demonstrate that LTRs can act as tissue-specific promoters and contribute to post-mitotic spermatogenic transcriptome diversity.

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Year of publication 2016

Yuvia A Pérez Rico, Valentina Boeva, Allison C Mallory, Angelo Bitetti, Sara Majello, Emmanuel Barillot, Alena Shkumatava (2016 Dec 15)

Comparative analyses of super-enhancers reveal conserved elements in vertebrate genomes.

Genome research : DOI : gr.203679.115 Learn more

Super-enhancers (SEs) are key transcriptional drivers of cellular, developmental and disease states in mammals, yet the conservational and regulatory features of these enhancer elements in non-mammalian vertebrates are unknown. To define SEs in zebrafish and enable sequence and functional comparisons to mouse and human SEs, we used genome-wide histone H3 lysine 27 acetylation (H3K27ac) occupancy as a primary SE delineator. Our study determined the set of SEs in pluripotent state cells and adult zebrafish tissues and revealed both similarities and differences between zebrafish and mammalian SEs. Although the total number of SEs was proportional to the genome size, the genomic distribution of zebrafish SEs differed from that of the mammalian SEs. Despite the evolutionary distance separating zebrafish and mammals and the low overall SE sequence conservation, ~42% of zebrafish SEs were located in close proximity to orthologs that also were associated with SEs in mouse and human. Compared to their non-associated counterparts, higher sequence conservation was revealed for those SEs that have maintained orthologous gene associations. Functional dissection of two of these SEs identified conserved sequence elements and tissue-specific expression patterns, while chromatin accessibility analyses predicted transcription factors governing the function of pluripotent state zebrafish SEs. Our zebrafish annotations and comparative studies show the extent of SE usage and their conservation across vertebrates, permitting future gene regulatory studies in several tissues.

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Maximilian Haeussler, Kai Schönig, Hélène Eckert, Alexis Eschstruth, Joffrey Mianné, Jean-Baptiste Renaud, Sylvie Schneider-Maunoury, Alena Shkumatava, Lydia Teboul, Jim Kent, Jean-Stephane Joly, Jean-Paul Concordet (2016 Jul 7)

Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR.

Genome biology : 148 : DOI : 10.1186/s13059-016-1012-2 Learn more

The success of the CRISPR/Cas9 genome editing technique depends on the choice of the guide RNA sequence, which is facilitated by various websites. Despite the importance and popularity of these algorithms, it is unclear to which extent their predictions are in agreement with actual measurements.

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