Imperial College London

ProfessorPetraHajkova

Faculty of MedicineInstitute of Clinical Sciences

Professor of Developmental Epigenetics
 
 
 
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Contact

 

+44 (0)20 3313 8264petra.hajkova Website

 
 
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Location

 

4006CRB (Clinical Research Building)Hammersmith Campus

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Summary

 

Publications

Publication Type
Year
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50 results found

Benesova M, Trejbalova K, Kucerova D, Vernerova Z, Hron T, Amouroux R, Klezl P, Hajkova P, Hejnar Jet al., Overexpression of TET dioxygenases in seminomas associates with low levels of DNA methylation and hydroxymethylation, Molecular Carcinogenesis, ISSN: 1098-2744

Germ cell tumors and particularly seminomas reflect the epigenomic features of their parental primordial germ cells, including the genomic DNA hypomethylation and expression of pluripotent cell markers. Because the DNA hypomethylation might be a result of TET dioxygenase activity, we examined expression of TET1-3 enzymes and the level of their product, 5-hydroxymethylcytosine, in a panel of histologically characterized seminomas and non-seminomatous germ cell tumors. Expression of TET dioxygenase mRNAs was quantified by real-time PCR. TET1 expression and the level of 5-hydroxymethylcytosine were examined immunohistochemically. Quantitative assessment of 5-methylcytosine and 5-hydroxymethylcytosine levels was done by liquid chromatography-mass spectroscopy technique. We found highly increased expression of TET1 dioxygenase in most seminomas and a strong TET1 staining in seminoma cells. Is ocitrate dehydrogenase 1 and 2 mutations were not detected suggest ing the enzymatic activity of TET1. The levels of 5-methylcytosine and 5-hydroxymethylcytosine in seminomas were found decreased in comparison to non-seminoma to us germ cell tumors and healthy testicular tissue. We propose TET1 expression as a marker of seminoma and mixed germ cell tumor and we suggest that high levels of TET1 expression are associated with the maintenance of low DNA methylation levels in seminomas. This “anti-methylator” phenotype of seminomas is in contrast to the CpG island methylator phenotype observed in a fraction of tumors of various types.

JOURNAL ARTICLE

Benesova M, Trejbalova K, Kucerova D, Vernerova Z, Hron T, Szabo A, Amouroux R, Klezl P, Hajkova P, Hejnar Jet al., 2017, Overexpression of TET dioxygenases in seminomas associates with low levels of DNA methylation and hydroxymethylation, MOLECULAR CARCINOGENESIS, Vol: 56, Pages: 1837-1850, ISSN: 0899-1987

JOURNAL ARTICLE

Ferry L, Fournier A, Tsusaka T, Adelmant G, Shimazu T, Matano S, Kirsh O, Amouroux R, Dohmae N, Suzuki T, Filion GJ, Deng W, de Dieuleveult M, Fritsch L, Kudithipudi S, Jeltsch A, Leonhardt H, Hajkova P, Marto JA, Arita K, Shinkai Y, Defossez P-Aet al., 2017, Methylation of DNA Ligase 1 by G9a/GLP Recruits UHRF1 to Replicating DNA and Regulates DNA Methylation, MOLECULAR CELL, Vol: 67, Pages: 550-+, ISSN: 1097-2765

JOURNAL ARTICLE

Izzo A, Ziegler-Birling C, Hill PWS, Brondani L, Hajkova P, Torres-Padilla M-E, Schneider Ret al., 2017, Dynamic changes in H1 subtype composition during epigenetic reprogramming., J Cell Biol

In mammals, histone H1 consists of a family of related proteins, including five replication-dependent (H1.1-H1.5) and two replication-independent (H1.10 and H1.0) subtypes, all expressed in somatic cells. To systematically study the expression and function of H1 subtypes, we generated knockin mouse lines in which endogenous H1 subtypes are tagged. We focused on key developmental periods when epigenetic reprogramming occurs: early mouse embryos and primordial germ cell development. We found that dynamic changes in H1 subtype expression and localization are tightly linked with chromatin remodeling and might be crucial for transitions in chromatin structure during reprogramming. Although all somatic H1 subtypes are present in the blastocyst, each stage of preimplantation development is characterized by a different combination of H1 subtypes. Similarly, the relative abundance of somatic H1 subtypes can distinguish male and female chromatin upon sex differentiation in developing germ cells. Overall, our data provide new insights into the chromatin changes underlying epigenetic reprogramming. We suggest that distinct H1 subtypes may mediate the extensive chromatin remodeling occurring during epigenetic reprogramming and that they may be key players in the acquisition of cellular totipotency and the establishment of specific cellular states.

JOURNAL ARTICLE

Wyck S, Herrera C, Requena-Torres C, Bittner L, Hajkova P, Bollwein H, Santoro Ret al., 2017, Oxidative stress in sperm causes developmental and epigenetic defects during bovine early embryonic development, 21st Annual Conference of the European-Society-for-Domestic-Animal-Reproduction (ESDAR), Publisher: WILEY, Pages: 143-143, ISSN: 0936-6768

CONFERENCE PAPER

Amouroux R, Nashun B, Shirane K, Nakagawa S, Hill PWS, D'Souza Z, Nakayama M, Matsuda M, Turp A, Ndjetehe E, Encheva V, Kudo NR, Koseki H, Sasaki H, Hajkova Pet al., 2016, De novo DNA methylation drives 5hmC accumulation in mouse zygotes, NATURE CELL BIOLOGY, Vol: 18, Pages: 225-+, ISSN: 1465-7392

JOURNAL ARTICLE

Eguizabal C, Herrera L, De Onate L, Montserrat N, Hajkova P, Belmonte JCIet al., 2016, Characterization of the Epigenetic Changes During Human Gonadal Primordial Germ Cells Reprogramming, STEM CELLS, Vol: 34, Pages: 2418-2428, ISSN: 1066-5099

JOURNAL ARTICLE

Leitch HG, Surani MA, Hajkova P, 2016, DNA (De)Methylation: The Passive Route to Naivety?, TRENDS IN GENETICS, Vol: 32, Pages: 592-595, ISSN: 0168-9525

JOURNAL ARTICLE

Trejbalova K, Benesova M, Kucerova D, Vernerova Z, Amouroux R, Hajkova P, Hejnar Jet al., 2016, Aberrant expression of ERVWE1 endogenous retrovirus and overexpression of TET dioxygenases are characteristic features of seminoma, Publisher: BIOMED CENTRAL LTD, ISSN: 1742-4690

CONFERENCE PAPER

Nashun B, Hill PW, Hajkova P, 2015, Reprogramming of cell fate: epigenetic memory and the erasure of memories past., EMBO Journal, Vol: 34, Pages: 1296-1308, ISSN: 0261-4189

Cell identity is a reflection of a cell type-specific gene expression profile, and consequently, cell type-specific transcription factor networks are considered to be at the heart of a given cellular phenotype. Although generally stable, cell identity can be reprogrammed in vitro by forced changes to the transcriptional network, the most dramatic example of which was shown by the induction of pluripotency in somatic cells by the ectopic expression of defined transcription factors alone. Although changes to cell fate can be achieved in this way, the efficiency of such conversion remains very low, in large part due to specific chromatin signatures constituting an epigenetic barrier to the transcription factor-mediated reprogramming processes. Here we discuss the two-way relationship between transcription factor binding and chromatin structure during cell fate reprogramming. We additionally explore the potential roles and mechanisms by which histone variants, chromatin remodelling enzymes, and histone and DNA modifications contribute to the stability of cell identity and/or provide a permissive environment for cell fate change during cellular reprogramming.

JOURNAL ARTICLE

Nashun B, Hill PWS, Smallwood SA, Dharmalingam G, Amouroux R, Clark SJ, Sharma V, Ndjetehe E, Pelczar P, Festenstein RJ, Kelsey G, Hajkova Pet al., 2015, Continuous Histone Replacement by Hira Is Essential for Normal Transcriptional Regulation and De Novo DNA Methylation during Mouse Oogenesis, MOLECULAR CELL, Vol: 60, Pages: 611-625, ISSN: 1097-2765

JOURNAL ARTICLE

Amouroux R, McEwen KR, Hajkova P, 2014, Current technological advances in mapping new DNA modifications, Drug Discovery Today: Disease Models, Vol: 12, Pages: 15-26, ISSN: 1740-6757

JOURNAL ARTICLE

Hill PS, Amouroux R, Hajkova P, 2014, DNA demethylation, Tet proteins and 5-hydroxymethylcytosine in epigenetic reprogramming: An emerging complex story, GENOMICS, Vol: 104, Pages: 324-333, ISSN: 0888-7543

JOURNAL ARTICLE

Supek F, Lehner B, Hajkova P, Warnecke Tet al., 2014, Hydroxymethylated Cytosines Are Associated with Elevated C to G Transversion Rates, PLOS GENETICS, Vol: 10, ISSN: 1553-7390

JOURNAL ARTICLE

Leitch HG, McEwen KR, Turp A, Encheva V, Carroll T, Grabole N, Mansfield W, Nashun B, Knezovich JG, Smith A, Surani MA, Hajkova Pet al., 2013, Naive pluripotency is associated with global DNA hypomethylation, NATURE STRUCTURAL & MOLECULAR BIOLOGY, Vol: 20, Pages: 311-316, ISSN: 1545-9993

JOURNAL ARTICLE

McEwen KR, Leitch HG, Amouroux R, Hajkova Pet al., 2013, The impact of culture on epigenetic properties of pluripotent stem cells and pre-implantation embryos, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 41, Pages: 711-719, ISSN: 0300-5127

JOURNAL ARTICLE

Piccolo FM, Bagci H, Brown KE, Landeira D, Soza-Ried J, Feytout A, Mooijman D, Hajkova P, Leitch HG, Tada T, Kriaucionis S, Dawlaty MM, Jaenisch R, Merkenschlager M, Fisher AGet al., 2013, Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion, MOLECULAR CELL, Vol: 49, Pages: 1023-1033, ISSN: 1097-2765

JOURNAL ARTICLE

Piccolo FM, Bagci H, Brown KE, Landeira D, Soza-Ried J, Feytout A, Mooijman D, Hajkova P, Leitch HG, Tada T, Kriaucionis S, Dawlaty MM, Jaenisch R, Merkenschlager M, Fisher AGet al., 2013, Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion., Molecular cell, Vol: 49, Pages: 1176-1176, ISSN: 1097-2765

JOURNAL ARTICLE

Hajkova P, 2011, Epigenetic reprogramming in the germline: towards the ground state of the epigenome, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 366, Pages: 2266-2273, ISSN: 0962-8436

JOURNAL ARTICLE

Hajkova P, 2010, Epigenetic reprogramming - taking a lesson from the embryo, CURRENT OPINION IN CELL BIOLOGY, Vol: 22, Pages: 342-350, ISSN: 0955-0674

JOURNAL ARTICLE

Hajkova P, Jeffries SJ, Lee C, Miller N, Jackson SP, Surani MAet al., 2010, Genome-Wide Reprogramming in the Mouse Germ Line Entails the Base Excision Repair Pathway, SCIENCE, Vol: 329, Pages: 78-82, ISSN: 0036-8075

JOURNAL ARTICLE

Surani MA, Hajkova P, 2010, Epigenetic reprogramming of mouse germ cells toward totipotency., Cold Spring Harb Symp Quant Biol, Vol: 75, Pages: 211-218

Primordial germ cells (PGCs), the precursors of sperm and eggs, are the route to totipotency and require establishment of a unique epigenome in this lineage. The genetic program for PGC specification in the mouse also initiates epigenetic reprogramming that continues when PGCs migrate into the developing gonads. Among these later events is active and genome-wide DNA demethylation, which is linked to extensive chromatin remodeling. These extensive epigenetic changes erase most, if not all, of the existing epigenetic information, which resets the epigenome for totipotency. Recent evidence suggests that active DNA demethylation involves a base excision repair (BER) pathway. BER is mechanistically linked to DNA demethylation, but what triggers BER is currently under investigation. The methylated cytosine (5mC) could be modified by deamination or to 5hmC, which could induce BER. Detection of Tet1 expression specifically and coincidentally, at the time of BER in PGCs, suggests that conversion of 5mC to 5hmC might be involved, at least in part, during epigenetic reprogramming and DNA demethylation in germ cells.

JOURNAL ARTICLE

Tee W-W, Pardo M, Theunissen TW, Yu L, Choudhary JS, Hajkova P, Surani MAet al., 2010, Prmt5 is essential for early mouse development and acts in the cytoplasm to maintain ES cell pluripotency, GENES & DEVELOPMENT, Vol: 24, Pages: 2772-2777, ISSN: 0890-9369

JOURNAL ARTICLE

Gebert C, Wrenzycki C, Herrmann D, Groeger D, Thiel J, Reinhardt R, Lehrach H, Hajkova P, Lucas-Hahn A, Carnwath JW, Niemann Het al., 2009, DNA methylation in the IGF2 intragenic DMR is re-established in a sex-specific manner in bovine blastocysts after somatic cloning, GENOMICS, Vol: 94, Pages: 63-69, ISSN: 0888-7543

JOURNAL ARTICLE

Hajkova P, Ancelin K, Waldmann T, Lacoste N, Lange UC, Cesari F, Lee C, Almouzni G, Schneider R, Surani MAet al., 2008, Chromatin dynamics during epigenetic reprogramming in the mouse germ line, NATURE, Vol: 452, Pages: 877-U6, ISSN: 0028-0836

JOURNAL ARTICLE

Hayashi K, Lopes SMCDS, Kaneda M, Tang F, Hajkova P, Lao K, O'Carroll D, Das PP, Tarakhovsky A, Miska EA, Surani MAet al., 2008, MicroRNA Biogenesis Is Required for Mouse Primordial Germ Cell Development and Spermatogenesis, PLOS ONE, Vol: 3, ISSN: 1932-6203

JOURNAL ARTICLE

Surani MA, Durcova-Hills G, Hajkova P, Hayashi K, Tee WWet al., 2008, Germ Line, Stem Cells, and Epigenetic Reprogramming, CONTROL AND REGULATION OF STEM CELLS, Vol: 73, Pages: 9-15, ISSN: 0091-7451

JOURNAL ARTICLE

Tang F, Hajkova P, O'Carroll D, Lee C, Tarakhovsky A, Lao K, Surani MAet al., 2008, MicroRNAs are tightly associated with RNA-induced gene silencing complexes in vivo, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 372, Pages: 24-29, ISSN: 0006-291X

JOURNAL ARTICLE

AZIM SURANI, ULRIKE LANGE, PETRA HAJKOVA, KATIA ANCELINet al., 2007, Epigenetic regulatory complex for control of gene expression

An epigenetic regulatory polypeptide complex comprises at least a first domain having site-specific DNA binding activity and at least a second domain having an arginine methyltransferase activity, wherein the second domain is capable of methylating an arginine residue located in the tail region of a histone H2A. The complex is able to regulate gene expression in cells, particularly in mammalian stem cells by controlling the methylation of R3 in the tail regions of histones H2A and H4. The complex is exemplified by a polypeptide complex comprising the DNA binding activity of Blimpi and the arginine methyltransferase activity of Prmt5.

JOURNAL ARTICLE

Surani MA, Hayashi K, Hajkova P, 2007, Genetic and epigenetic regulators of pluripotency, CELL, Vol: 128, Pages: 747-762, ISSN: 0092-8674

JOURNAL ARTICLE

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