Publications by authors named "Yuvia A Pérez-Rico"

6 Publications

  • Page 1 of 1

Bioinformatic Analysis of Single-Cell Hi-C Data from Early Mouse Embryo.

Methods Mol Biol 2021 ;2214:295-316

Institut Curie, CNRS UMR3215/ INSERM U934, Paris Sciences & Lettres Research University (PSL), Paris, France.

The adaptation of Hi-C protocols to enable the investigation of chromosome organization in single cells opens new avenues to study the dynamics of this process during embryogenesis. However, the analysis of single-cell Hi-C data is not yet standardized and raises novel bioinformatic challenges. Here we describe a complete workflow for the analysis of single-cell Hi-C data, with a main focus on allele-specific analysis based on data obtained from hybrid embryos.
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http://dx.doi.org/10.1007/978-1-0716-0958-3_20DOI Listing
January 2021

SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation.

Nature 2020 08 16;584(7822):635-639. Epub 2020 Jul 16.

Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.

In mammals, the acquisition of the germline from the soma provides the germline with an essential challenge: the need to erase and reset genomic methylation. In the male germline, RNA-directed DNA methylation silences young, active transposable elements. The PIWI protein MIWI2 (PIWIL4) and its associated PIWI-interacting RNAs (piRNAs) instruct DNA methylation of transposable elements. piRNAs are proposed to tether MIWI2 to nascent transposable element transcripts; however, the mechanism by which MIWI2 directs the de novo methylation of transposable elements is poorly understood, although central to the immortality of the germline. Here we define the interactome of MIWI2 in mouse fetal gonocytes undergoing de novo genome methylation and identify a previously unknown MIWI2-associated factor, SPOCD1, that is essential for the methylation and silencing of young transposable elements. The loss of Spocd1 in mice results in male-specific infertility but does not affect either piRNA biogenesis or the localization of MIWI2 to the nucleus. SPOCD1 is a nuclear protein whose expression is restricted to the period of de novo genome methylation. It co-purifies in vivo with DNMT3L and DNMT3A, components of the de novo methylation machinery, as well as with constituents of the NURD and BAF chromatin remodelling complexes. We propose a model whereby tethering of MIWI2 to a nascent transposable element transcript recruits repressive chromatin remodelling activities and the de novo methylation apparatus through SPOCD1. In summary, we have identified a previously unrecognized and essential executor of mammalian piRNA-directed DNA methylation.
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http://dx.doi.org/10.1038/s41586-020-2557-5DOI Listing
August 2020

Demarcation of Topologically Associating Domains Is Uncoupled from Enriched CTCF Binding in Developing Zebrafish.

iScience 2020 May 10;23(5):101046. Epub 2020 Apr 10.

Institut Curie PSL Research University, INSERM U934, CNRS UMR 3215 75005, Paris, France. Electronic address:

CCCTC-binding factor (CTCF) is a conserved architectural protein that plays crucial roles in gene regulation and three-dimensional (3D) chromatin organization. To better understand mechanisms and evolution of vertebrate genome organization, we analyzed genome occupancy of CTCF in zebrafish utilizing an endogenously epitope-tagged CTCF knock-in allele. Zebrafish CTCF shares similar facets with its mammalian counterparts, including binding to enhancers, active promoters and repeat elements, and bipartite sequence motifs of its binding sites. However, we found that in vivo CTCF binding is not enriched at boundaries of topologically associating domains (TADs) in developing zebrafish, whereas TAD demarcation by chromatin marks did not differ from mammals. Our data suggest that general mechanisms underlying 3D chromatin organization, and in particular the involvement of CTCF in this process, differ between distant vertebrate species.
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http://dx.doi.org/10.1016/j.isci.2020.101046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182764PMC
May 2020

MicroRNA degradation by a conserved target RNA regulates animal behavior.

Nat Struct Mol Biol 2018 03 26;25(3):244-251. Epub 2018 Feb 26.

Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France.

microRNAs (miRNAs) repress target transcripts through partial complementarity. By contrast, highly complementary miRNA-binding sites within viral and artificially engineered transcripts induce miRNA degradation in vitro and in cell lines. Here, we show that a genome-encoded transcript harboring a near-perfect and deeply conserved miRNA-binding site for miR-29 controls zebrafish and mouse behavior. This transcript originated in basal vertebrates as a long noncoding RNA (lncRNA) and evolved to the protein-coding gene NREP in mammals, where the miR-29-binding site is located within the 3' UTR. We show that the near-perfect miRNA site selectively triggers miR-29b destabilization through 3' trimming and restricts its spatial expression in the cerebellum. Genetic disruption of the miR-29 site within mouse Nrep results in ectopic expression of cerebellar miR-29b and impaired coordination and motor learning. Thus, we demonstrate an endogenous target-RNA-directed miRNA degradation event and its requirement for animal behavior.
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http://dx.doi.org/10.1038/s41594-018-0032-xDOI Listing
March 2018

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

Genome Res 2017 02 13;27(2):259-268. Epub 2016 Dec 13.

Institut Curie, PSL Research University, INSERM U934, CNRS UMR 3215, F-75005, Paris, France.

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 nonmammalian 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 nonassociated 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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http://dx.doi.org/10.1101/gr.203679.115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287231PMC
February 2017

Stem cell-dependent formation of a functional anterior regeneration pole in planarians requires Zic and Forkhead transcription factors.

Dev Biol 2014 Jun 1;390(2):136-48. Epub 2014 Apr 1.

Max Planck Research Group Stem Cells & Regeneration, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Str. 54, 48149 Münster, Germany; Medical Faculty, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany. Electronic address:

Planarians can regenerate their head within days. This process depends on the direction of adult stem cells to wound sites and the orchestration of their progenitors to commit to appropriate lineages and to arrange into patterned tissues. We identified a zinc finger transcription factor, Smed-ZicA, as a downstream target of Smed-FoxD, a Forkhead transcription factor required for head regeneration. Smed-zicA and Smed-FoxD are co-expressed with the Wnt inhibitor notum and the Activin inhibitor follistatin in a cluster of cells at the anterior-most tip of the regenerating head - the anterior regeneration pole - and in surrounding stem cell progeny. Depletion of Smed-zicA and Smed-FoxD by RNAi abolishes notum and follistatin expression at the pole and inhibits head formation downstream of initial polarity decisions. We suggest a model in which ZicA and FoxD transcription factors synergize to control the formation of Notum- and Follistatin-producing anterior pole cells. Pole formation might constitute an early step in regeneration, resulting in a signaling center that orchestrates cellular events in the growing tissue.
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http://dx.doi.org/10.1016/j.ydbio.2014.03.016DOI Listing
June 2014