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
to

53 results found

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

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Tang F, Kaneda M, O'Carroll D, Hajkova P, Barton SC, Sun YA, Lee C, Tarakhovsky A, Lao K, Surani MAet al., 2007, Maternal microRNAs are essential for mouse zygotic development, GENES & DEVELOPMENT, Vol: 21, Pages: 644-648, ISSN: 0890-9369

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Ancelin K, Lange UC, Hajkova P, Schneider R, Bannister AJ, Kouzarides T, Surani MAet al., 2006, Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells, NATURE CELL BIOLOGY, Vol: 8, Pages: 623-630, ISSN: 1465-7392

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Durcova-Hills G, Hajkova P, Sullivan S, Barton S, Surani MA, McLaren Aet al., 2006, Influence of sex chromosome constitution on the genomic imprinting of germ cells, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 103, Pages: 11184-11188, ISSN: 0027-8424

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Gebert C, Wrenzycki C, Herrmann D, Groeger D, Reinhardt R, Hajkova P, Lucas-Hahn A, Carnwath J, Lehrach H, Niemann Het al., 2006, The bovine IGF2 gene is differentially methylated in oocyte and sperm DNA, GENOMICS, Vol: 88, Pages: 222-229, ISSN: 0888-7543

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Miyoshi N, Barton SC, Kaneda M, Hajkova P, Surani MAet al., 2006, The continuing quest to comprehend genomic imprinting, CYTOGENETIC AND GENOME RESEARCH, Vol: 113, Pages: 6-11, ISSN: 1424-8581

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Tang F, Hajkova P, Barton SC, O'Carroll D, Lee C, Lao K, Surani MAet al., 2006, 220-plex microRNA expression profile of a single cell, NATURE PROTOCOLS, Vol: 1, Pages: 1154-1159, ISSN: 1754-2189

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Tang FC, Hajkova P, Barton SC, Lao KQ, Surani MAet al., 2006, MicroRNA expression profiling of single whole embryonic stem cells, NUCLEIC ACIDS RESEARCH, Vol: 34, ISSN: 0305-1048

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Tykocinski LO, Hajkova P, Chang HD, Stamm T, Sozeri O, Lohning M, Hu-Li J, Niesner U, Kreher S, Friedrich B, Pannetier C, Grutz G, Walter J, Paul WE, Radbruch Aet al., 2005, A critical control element for interleukin-4 memory expression in T helper lymphocytes, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 280, Pages: 28177-28185, ISSN: 0021-9258

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Western P, Maldonado-Saldivia J, van den Bergen J, Hajkova P, Saitou M, Barton S, Surani MAet al., 2005, Analysis of Esg1 expression in pluripotent cells and the germline reveals similarities with Oct4 and Sox2 and differences between human pluripotent cell lines., Stem Cells, Vol: 23, Pages: 1436-1442, ISSN: 1066-5099

Establishment of pluripotent epiblast cells is a critical event during early mammalian development because all somatic lineages and the primordial germ cells (PGCs) are derived from them. The epiblast and PGCs are in turn the precursors of pluripotent embryonic stem cells and embryonic germ cells, respectively. Although PGCs are specialized cells, they express several key pluripotency-related genes, such as Oct4 and Sox2. We have analyzed Esg1 expression in mouse and human cells and shown that in the mouse the gene is specifically expressed in preimplantation embryos, stem cells, and the germline. Moreover, Esg1 coexpresses with Oct4 and Sox2, confirming its identity as a marker of the pluripotent cycle. Esg1 is also expressed with Oct4 and Sox2 by human embryonic stem cells and in germ cell carcinoma tissue but not by all human embryonal carcinoma cell lines. These data suggest that together with Oct4 and Sox2, Esg1 plays a conserved role in the pluripotent pathway of mouse and human stem and germ cells.

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Hajkova P, Surani MA, 2004, Development. Programming the X chromosome., Science, Vol: 303, Pages: 633-634

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Surani MA, Ancelin K, Hajkova P, Lange UC, Payer B, Western P, Saitou Met al., 2004, Mechanism of mouse germ cell specification: a genetic program regulating epigenetic reprogramming., Cold Spring Harb Symp Quant Biol, Vol: 69, Pages: 1-9, ISSN: 0091-7451

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Hejnar J, Elleder D, Hajkova P, Walter J, Blazkova J, Svoboda Jet al., 2003, Demethylation of host-cell DNA at the site of avian retrovirus integration, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 311, Pages: 641-648, ISSN: 0006-291X

JOURNAL ARTICLE

Lane N, Dean W, Erhardt S, Hajkova P, Surani A, Walter J, Reik Wet al., 2003, Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse, GENESIS, Vol: 35, Pages: 88-93, ISSN: 1526-954X

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Lopes S, Lewis A, Hajkova R, Dean W, Oswald J, Forne T, Murrell A, Constancia M, Bartolomei M, Walter J, Reik Wet al., 2003, Epigenetic modifications in an imprinting cluster are controlled by a hierarchy of DMRs suggesting long-range chromatin interactions, HUMAN MOLECULAR GENETICS, Vol: 12, Pages: 295-305, ISSN: 0964-6906

JOURNAL ARTICLE

Tykocinski L, Hajkova P, Stamm T, Sözeri O, Löhning M, Friedrich B, Hu-Li J, Pannetier C, Paul WE, Grütz G, Walter J, Radbruch Aet al., 2003, A GATA-3 binding site in the first intron of the interleukin-4 gene defines a critical element for the memory expression of interleukin-4 in Th lymphocytes., Arthritis research & therapy, Vol: 5, Pages: 61-61, ISSN: 1478-6354

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Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, Walter J, Surani MAet al., 2002, Epigenetic reprogramming in mouse primordial germ cells., Mech Dev, Vol: 117, Pages: 15-23, ISSN: 0925-4773

Genome-wide epigenetic reprogramming in mammalian germ cells, zygote and early embryos, plays a crucial role in regulating genome functions at critical stages of development. We show here that mouse primordial germ cells (PGCs) exhibit dynamic changes in epigenetic modifications between days 10.5 and 12.5 post coitum (dpc). First, contrary to previous suggestions, we show that PGCs do indeed acquire genome-wide de novo methylation during early development and migration into the genital ridge. However, following their entry into the genital ridge, there is rapid erasure of DNA methylation of regions within imprinted and non-imprinted loci. For most genes, the erasure commences simultaneously in PGCs in both male and female embryos, which is completed within 1 day of development. Based on the kinetics of this process, we suggest that this is an active demethylation process initiated upon the entry of PGCs into the gonadal anlagen. The timing of reprogramming in PGCs is crucial since it ensures that germ cells of both sexes acquire an equivalent epigenetic state prior to the differentiation of the definitive male and female germ cells in which new parental imprints are established subsequently. Some repetitive elements, however, show incomplete erasure, which may be essential for chromosome stability and for preventing activation of transposons to reduce the risk of germline mutations. Aberrant epigenetic reprogramming in the germ line would cause the inheritance of epimutations that may have consequences for human diseases as suggested by studies on mouse models.

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Hajkova P, el-Maarri O, Engemann S, Oswald J, Olek A, Walter Jet al., 2002, DNA-methylation analysis by the bisulfite-assisted genomic sequencing method., Methods Mol Biol, Vol: 200, Pages: 143-154, ISSN: 1064-3745

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Engemann S, El-Maarri O, Hajkova P, Oswald J, Walter Jet al., 2001, Bisulfite-based methylation analysis of imprinted genes., Methods Mol Biol, Vol: 181, Pages: 217-228

Genomic imprinting is an epigenetically controlled form of gene regulation leading to the preferential expression of one parental gene copy. To date, approximately 40 imprinted genes have been described that are exclusively or predominantly expressed from either the paternal or the maternal allele (www.mgu.har.mrc.ac.uk/imprinting/implink.html). Changes in the imprinted expression of such genes result in developmental abnormalities; in the human they are associated with several diseases and various types of cancer (1-3).

JOURNAL ARTICLE

Hejnar J, Hájková P, Plachy J, Elleder D, Stepanets V, Svoboda Jet al., 2001, CpG island protects Rous sarcoma virus-derived vectors integrated into nonpermissive cells from DNA methylation and transcriptional suppression., Proc Natl Acad Sci U S A, Vol: 98, Pages: 565-569, ISSN: 0027-8424

CpG islands are important in the protection of adjacent housekeeping genes from de novo DNA methylation and for keeping them in a transcriptionally active state. However, little is known about their capacity to protect heterologous genes and assure position-independent transcription of adjacent transgenes or retroviral vectors. To tackle this question, we have used the mouse aprt CpG island to flank a Rous sarcoma virus (RSV)-derived reporter vector and followed the transcriptional activity of integrated vectors. RSV is an avian retrovirus which does not replicate in mammalian cells because of several blocks at all levels of the replication cycle. Here we show that our RSV-derived reporter proviruses linked to the mouse aprt gene CpG island remain undermethylated and keep their transcriptional activity after stable transfection into both avian and nonpermissive mammalian cells. This effect is most likely caused by the protection from de novo methylation provided by the CpG island and not by enhancement of the promoter strength. Our results are consistent with previous finding of CpG islands in proximity to active but not inactive proviruses and support further investigation of the protection of the gene transfer vectors from DNA methylation.

JOURNAL ARTICLE

Machon O, Hejnar J, Hájková P, Geryk J, Svoboda Jet al., 1996, The LTR, v-src, LTR provirus in H-19 hamster tumor cell line is integrated adjacent to the negative regulatory region., Gene, Vol: 174, Pages: 9-17, ISSN: 0378-1119

The tumor hamster cell line H-19 harbors a single copy LTR, v-src, LTR provirus that becomes permanently transcriptionally suppressed in morphological revertants segregating at high rate from this cell line. Our previous data document that the provirus suppression is mediated by epigenetic cell-regulatory mechanisms. In this report, we concentrate on cellular sequences neighboring the integration site. The locus is unique for Syrian hamster and is not detectable in DNA of several animal species. No restriction sites that usually hint at the presence of CpG islands were found in the significantly close vicinity of the provirus. Nevertheless, the chromosomal DNA flanking the provirus is rich in GC content (57.8%). We localized a 0.5-kb region downstream from the provirus that remarkably inhibits transcription in the transient expression assay and is effective both on the homologous RSV LTR promoter/enhancer and heterologous SV40 promoter. We propose that a cellular trans-acting factor is involved in the silencing of the reporter gene. Since this activity is comparable both in transformed and revertant cells, we speculate that this down-regulatory region makes the permissive integration locus prone to provirus silencing initiated by other fluctuating stimuli.

JOURNAL ARTICLE

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

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