Angèle Santenard

Publications (3)36.15 Total impact

• Article: Heterochromatin formation in the mouse embryo requires critical residues of the histone variant H3.3.

  Angèle Santenard, Céline Ziegler-Birling, Marc Koch, Làszlò Tora, Andrew J Bannister, Maria-Elena Torres-Padilla
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  ABSTRACT: In mammals, oocyte fertilization by sperm initiates development. This is followed by epigenetic reprogramming of both parental genomes, which involves the de novo establishment of chromatin domains. In the mouse embryo, methylation of histone H3 establishes an epigenetic asymmetry and is predominant in the maternal pronucleus. However, the roles of differential incorporation of histone H3 variants in the parental chromatin, and of modified residues within specific histone variants, have not been addressed. Here we show that the histone variant H3.3, and in particular lysine 27, is required for the establishment of heterochromatin in the mouse embryo. H3.3 localizes to paternal pericentromeric chromatin during S phase at the time of transcription of pericentromeric repeats. Mutation of H3.3 K27, but not of H3.1 K27, results in aberrant accumulation of pericentromeric transcripts, HP1 mislocalization, dysfunctional chromosome segregation and developmental arrest. This phenotype is rescued by injection of double-stranded RNA (dsRNA) derived from pericentromeric transcripts, indicating a functional link between H3.3K27 and the silencing of such regions by means of an RNA-interference (RNAi) pathway. Our work demonstrates a role for a modifiable residue within a histone-variant-specific context during reprogramming and identifies a novel function for mammalian H3.3 in the initial formation of dsRNA-dependent heterochromatin.
  Nature Cell Biology 09/2010; 12(9):853-62. · 19.49 Impact Factor
• Source

  Available from: Gioia Altobelli

  Article: TBP2 is essential for germ cell development by regulating transcription and chromatin condensation in the oocyte.

  Emese Gazdag, Angèle Santenard, Céline Ziegler-Birling, Gioia Altobelli, Olivier Poch, Làszlò Tora, Maria-Elena Torres-Padilla
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  ABSTRACT: Development of the germline requires consecutive differentiation events. Regulation of these has been associated with germ cell-specific and pluripotency-associated transcription factors, but the role of general transcription factors (GTFs) remains elusive. TATA-binding protein (TBP) is a GTF involved in transcription by all RNA polymerases. During ovarian folliculogenesis in mice the vertebrate-specific member of the TBP family, TBP2/TRF3, is expressed exclusively in oocytes. To determine TBP2 function in vivo, we generated TBP2-deficient mice. We found that Tbp2(-/-) mice are viable with no apparent phenotype. However, females lacking TBP2 are sterile due to defective folliculogenesis, altered chromatin organization, and transcriptional misregulation of key oocyte-specific genes. TBP2 binds to promoters of misregulated genes, suggesting that TBP2 directly regulates their expression. In contrast, TBP ablation in the female germline results in normal ovulation and fertilization, indicating that in these cells TBP is dispensable. We demonstrate that TBP2 is essential for the differentiation of female germ cells, and show the mutually exclusive functions of these key core promoter-binding factors, TBP and TBP2, in the mouse.
  Genes & development 09/2009; 23(18):2210-23. · 12.08 Impact Factor
• Source

  Available from: inserm.fr

  Article: Epigenetic reprogramming in mammalian reproduction: contribution from histone variants.

  Angèle Santenard, Maria-Elena Torres-Padilla
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  ABSTRACT: Development of the mammalian embryo is, by definition, epigenetic. At the level of the nucleosome, the building block of the chromatin, changes in chromatin structure can be regulated through histone content. Apart from the canonical histones whose synthesis is restricted to S-phase, different histone variants have been identified. Histone variants can help to establish specialised chromatin regions and to regulate developmental and cell differentiation processes. While the role of histone variants has been extensively explored in differentiated cells, less is known in germ cells and embryos. Increasing lines of evidence suggest that the functions and/or properties of histone variants in embryos might be different to those in somatic cells. During reprogramming, histone variants such as H3.3 or H2A.Z are candidates to play potential important roles. We suggest that H3.3 has an important role in setting up a 'transition' signature, and provides the possibility to infer changes in chromatin architecture independent of DNA replication. This should confer flexibility during important developmental processes. The specific pathways through which H3.3 could regulate different chromatin conformations at different loci and the identification of specific proteins responsible for this deposition are an important challenge for future investigation. Lastly, the set of variants incorporated within the nucleosome can have important consequences in the regulation of epigenetic mechanisms during development.
  Epigenetics: official journal of the DNA Methylation Society 03/2009; 4(2):80-4. · 4.58 Impact Factor