Imperial College London

DrMichellePercharde

Faculty of MedicineInstitute of Clinical Sciences

Honorary Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 8299m.percharde Website

 
 
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Location

 

CRB 2006 / 2013Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

17 results found

Xie SQ, Leeke BJ, Whidling C, Wagner RT, Garcia-Llagostera F, Chammas P, Cheung NT-F, Dormann D, McManus MT, Percharde Met al., 2021, Nucleolar-based <i>Dux</i> repression is essential for 2-cell stage exit

<jats:title>Abstract</jats:title><jats:p>Upon fertilisation, the mammalian embryo must switch from dependence on maternal transcripts to transcribing its own genome, and in mice involves the transient upregulation of MERVL transposons and MERVL-driven genes at the 2-cell stage. The mechanisms and requirement for MERVL and 2-cell (2C) gene upregulation are poorly understood. Moreover, this MERVL-driven transcriptional program must be rapidly shut off to allow 2C exit and developmental progression. Here, we report that robust ribosomal RNA (rRNA) synthesis and nucleolar maturation are essential for exit from the 2C state. 2C-like cells and 2C embryos show similar immature nucleoli with altered structure and reduced rRNA output. We reveal that nucleolar disruption via blocking Pol I activity or preventing nucleolar phase separation enhances conversion to a 2C-like state in embryonic stem cells (ESCs) by detachment of the MERVL activator <jats:italic>Dux</jats:italic> from the nucleolar surface. In embryos, nucleolar disruption prevents proper <jats:italic>Dux</jats:italic> silencing and leads to 2-4 cell arrest. Our findings reveal an intriguing link between rRNA synthesis, nucleolar maturation and gene repression during early development.</jats:p>

Journal article

Percharde M, Lin C-J, Ramalho-Santos M, 2021, Depletion of nuclear LINE1 RNA in mouse ESCs and embryos., STAR Protoc, Vol: 2

LINE1 is the most active and abundant family of retrotransposons; it is implicated in a number of pathologies, as well as in early embryo development. We present a protocol to specifically knockdown LINE1 in mouse embryonic stem cells and embryos, including details for the nucleofection and zygote microinjection of LINE antisense oligos, followed by RNA FISH validation. This protocol can be used in development, as well as other cell types where LINE1 is believed to be expressed. For complete information on the use and execution of this protocol, please refer to Percharde et al. (2018).

Journal article

Lu JY, Chang L, Li T, Wang T, Yin Y, Zhan G, Han X, Zhang K, Tao Y, Percharde M, Wang L, Peng Q, Yan P, Zhang H, Bi X, Shao W, Hong Y, Wu Z, Ma R, Wang P, Li W, Zhang J, Chang Z, Hou Y, Zhu B, Ramalho-Santos M, Li P, Xie W, Na J, Sun Y, Shen Xet al., 2021, Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome, CELL RESEARCH, Vol: 31, Pages: 613-630, ISSN: 1001-0602

Journal article

Kuwahara A, Lewis AE, Coombes C, Leung F-S, Percharde M, Bush JOet al., 2020, Delineating the early transcriptional specification of the mammalian trachea and esophagus, ELIFE, Vol: 9, ISSN: 2050-084X

Journal article

Lu JY, Shao W, Chang L, Yin Y, Li T, Zhang H, Hong Y, Percharde M, Guo L, Wu Z, Liu L, Liu W, Yan P, Ramalho-Santos M, Sun Y, Shen Xet al., 2020, Genomic Repeats Categorize Genes with Distinct Functions for Orchestrated Regulation, CELL REPORTS, Vol: 30, Pages: 3296-+, ISSN: 2211-1247

Journal article

Percharde M, Sultana T, Ramalho-Santos M, 2020, What Doesn't Kill You Makes You Stronger: Transposons as Dual Players in Chromatin Regulation and Genomic Variation, BIOESSAYS, Vol: 42, ISSN: 0265-9247

Journal article

Lu JY, Chang L, Li T, Wang T, Yin Y, Zhan G, Zhang K, Percharde M, Wang L, Peng Q, Yan P, Zhang H, Han X, Bi X, Shao W, Hong Y, Wu Z, Wang P, Li W, Zhang J, Chang Z, Hou Y, Li P, Ramalho-Santos M, Na J, Xie W, Sun Y, Shen Xet al., 2019, L1 and B1 repeats blueprint the spatial organization of chromatin

<jats:title>SUMMARY</jats:title><jats:p>Despite extensive mapping of three-dimensional (3D) chromatin structures, the basic principles underlying genome folding remain unknown. Here, we report a fundamental role for L1 and B1 retrotransposons in shaping the macroscopic 3D genome structure. Homotypic clustering of B1 and L1 repeats in the nuclear interior or at the nuclear and nucleolar peripheries, respectively, segregates the genome into mutually exclusive nuclear compartments. This spatial segregation of L1 and B1 is conserved in mouse and human cells, and occurs dynamically during establishment of the 3D chromatin structure in early embryogenesis and the cell cycle. Depletion of L1 transcripts drastically disrupts the spatial distributions of L1- and B1-rich compartments. L1 transcripts are strongly associated with L1 DNA sequences and induce phase separation of the heterochromatin protein HP1α. Our results suggest that genomic repeats act as the blueprint of chromatin macrostructure, thus explaining the conserved higher-order structure of chromatin across mammalian cells.</jats:p>

Journal article

DiTroia SP, Percharde M, Guerquin M-J, Wall E, Collignon E, Ebata KT, Mesh K, Mahesula S, Agathocleous M, Laird DJ, Livera G, Ramalho-Santos Met al., 2019, Maternal vitamin C regulates reprogramming of DNA methylation and germline development, NATURE, Vol: 573, Pages: 271-+, ISSN: 0028-0836

Journal article

Percharde M, Lin C-J, Yin Y, Guan J, Peixoto GA, Bulut-Karslioglu A, Biechele S, Huang B, Shen X, Ramalho-Santos Met al., 2018, A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity, CELL, Vol: 174, Pages: 391-+, ISSN: 0092-8674

Journal article

Bulut-Karslioglu A, Macrae TA, Oses-Prieto JA, Covarrubias S, Percharde M, Ku G, Diaz A, McManus MT, Burlingame AL, Ramalho-Santos Met al., 2018, The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output, CELL STEM CELL, Vol: 22, Pages: 369-+, ISSN: 1934-5909

Journal article

Bulut-Karslioglu A, Macrae TA, Oses-Prieto JA, Covarrubias S, Percharde M, Ku G, Diaz A, McManus MT, Burlingame AL, Ramalho-Santos Met al., 2017, The transcriptionally permissive chromatin state of ES cells is acutely tuned to translational output

<jats:title>SUMMARY</jats:title><jats:p>A permissive chromatin environment coupled to hypertranscription is critical to drive the rapid proliferation of Embryonic Stem (ES) cells and peri-implantation embryos. We carried out a genome-wide screen to systematically dissect the regulation of the euchromatic state of ES cells. The results reveal that activity of cellular growth pathways, prominently protein synthesis, perpetuates the euchromatic state and hypertranscription of ES cells. Acute, mild inhibition of translation results in rapid depletion of euchromatic marks in ES cells and blastocysts, concurrent with delocalization of RNA polymerase II and reduction in nascent transcription. Remarkably, reduced translational output leads to rewiring of open chromatin within 3 hours, including decreased accessibility at a subset of active developmental enhancers and increased accessibility at histone genes and transposable elements. Using a proteome-scale analysis, we show that several euchromatin regulators are unstable proteins and thus continuously depend on a high translational output. We propose that this mechanistic interdependence of euchromatin, transcription and translation sets the pace of proliferation at peri-implantation and may be employed generally by stem/progenitor cells.</jats:p>

Journal article

Percharde M, Wong P, Ramalho-Santos M, 2017, Global Hypertranscription in the Mouse Embryonic Germline, CELL REPORTS, Vol: 19, Pages: 1987-1996, ISSN: 2211-1247

Journal article

Percharde M, Bulut-Karslioglu A, Ramalho-Santos M, 2017, Hypertranscription in Development, Stem Cells, and Regeneration, DEVELOPMENTAL CELL, Vol: 40, Pages: 9-21, ISSN: 1534-5807

Journal article

Qin H, Hejna M, Liu Y, Percharde M, Wossidlo M, Blouin L, Durruthy-Durruthy J, Wong P, Qi Z, Yu J, Qi LS, Sebastiano V, Song JS, Ramalho-Santos Met al., 2016, YAP Induces Human Naive Pluripotency, CELL REPORTS, Vol: 14, Pages: 2301-2312, ISSN: 2211-1247

Journal article

Percharde M, Azuara V, 2013, Essential roles for the nuclear receptor coactivator Ncoa3 in pluripotency, CELL CYCLE, Vol: 12, Pages: 195-196, ISSN: 1538-4101

Journal article

Percharde M, Lavial F, Ng J-H, Kumar V, Tomaz RA, Martin N, Yeo J-C, Gil J, Prabhakar S, Ng H-H, Parker MG, Azuara Vet al., 2012, Ncoa3 functions as an essential Esrrb coactivator to sustain embryonic stem cell self-renewal and reprogramming, GENES & DEVELOPMENT, Vol: 26, Pages: 2286-2298, ISSN: 0890-9369

Journal article

Lopez J, Percharde M, Coley HM, Webb A, Crook Tet al., 2009, The context and potential of epigenetics in oncology, BRITISH JOURNAL OF CANCER, Vol: 100, Pages: 571-577, ISSN: 0007-0920

Journal article

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