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Papers by Sophie Chantalat

Research paper thumbnail of A Novel Golgi Membrane Protein Is a Partner of the ARF Exchange Factors Gea1p and Gea2p

Molecular Biology of the Cell, 2003

The Sec7 domain guanine nucleotide exchange factors (GEFs) for the GTPase ARF are highly conserve... more The Sec7 domain guanine nucleotide exchange factors (GEFs) for the GTPase ARF are highly conserved regulators of membrane dynamics and protein trafficking. The interactions of large ARF GEFs with cellular membranes for localization and/or activation are likely to participate in regulated recruitment of ARF and effectors. However, these interactions remain largely unknown.

Research paper thumbnail of The Arf activator Gea2p and the P-type ATPase Drs2p interact at the Golgi in Saccharomyces cerevisiae

Journal of Cell Science, 2004

Research paper thumbnail of Ftx is a non-coding RNA which affects Xist expression and chromatin structure within the X-inactivation center region

Human Molecular Genetics, 2011

X chromosome inactivation (XCI) is an essential epigenetic process which involves several non-cod... more X chromosome inactivation (XCI) is an essential epigenetic process which involves several non-coding RNAs (ncRNAs), including Xist, the master regulator of X-inactivation initiation. Xist is flanked in its 5' region by a large heterochromatic hotspot, which contains several transcription units including a gene of unknown function, Ftx (five prime to Xist). In this article, we describe the characterization and functional analysis of murine Ftx. We present evidence that Ftx produces a conserved functional long ncRNA, and additionally hosts microRNAs (miR) in its introns. Strikingly, Ftx partially escapes X-inactivation and is upregulated specifically in female ES cells at the onset of X-inactivation, an expression profile which closely follows that of Xist. We generated Ftx null ES cells to address the function of this gene. In these cells, only local changes in chromatin marks are detected within the hotspot, indicating that Ftx is not involved in the global maintenance of the heterochromatic structure of this region. The Ftx mutation, however, results in widespread alteration of transcript levels within the X-inactivation center (Xic) and particularly important decreases in Xist RNA levels, which were correlated with increased DNA methylation at the Xist CpG island. Altogether our results indicate that Ftx is a positive regulator of Xist and lead us to propose that Ftx is a novel ncRNA involved in XCI.

Research paper thumbnail of Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin

Genome Research, 2011

The mammalian genome contains numerous regions known as facultative heterochromatin, which contri... more The mammalian genome contains numerous regions known as facultative heterochromatin, which contribute to transcriptional silencing during development and cell differentiation. We have analyzed the pattern of histone modifications associated with facultative heterochromatin within the mouse imprinted Snurf-Snrpn cluster, which is homologous to the human Prader-Willi syndrome genomic region. We show here that the maternally inherited Snurf-Snrpn 3-Mb region, which is silenced by a potent transcription repressive mechanism, is uniformly enriched in histone methylation marks usually found in constitutive heterochromatin, such as H4K20me3, H3K9me3, and H3K79me3. Strikingly, we found that trimethylated histone H3 at lysine 36 (H3K36me3), which was previously identified as a hallmark of actively transcribed regions, is deposited onto the silenced, maternally contributed 3-Mb imprinted region. We show that H3K36me3 deposition within this large heterochromatin domain does not correlate with transcription events, suggesting the existence of an alternative pathway for the deposition of this histone modification. In addition, we demonstrate that H3K36me3 is markedly enriched at the level of pericentromeric heterochromatin in mouse embryonic stem cells and fibroblasts. This result indicates that H3K36me3 is associated with both facultative and constitutive heterochromatin. Our data suggest that H3K36me3 function is not restricted to actively transcribed regions only and may contribute to the composition of heterochromatin, in combination with other histone modifications.

Research paper thumbnail of A role for non-coding Tsix transcription in partitioning chromatin domains within the mouse X-inactivation centre

Epigenetics & Chromatin, 2009

Background: Delimiting distinct chromatin domains is essential for temporal and spatial regulatio... more Background: Delimiting distinct chromatin domains is essential for temporal and spatial regulation of gene expression. Within the X-inactivation centre region (Xic), the Xist locus, which triggers X-inactivation, is juxtaposed to a large domain of H3K27 trimethylation (H3K27me3).

Research paper thumbnail of A Novel Golgi Membrane Protein Is a Partner of the ARF Exchange Factors Gea1p and Gea2p

Molecular Biology of the Cell, 2003

The Sec7 domain guanine nucleotide exchange factors (GEFs) for the GTPase ARF are highly conserve... more The Sec7 domain guanine nucleotide exchange factors (GEFs) for the GTPase ARF are highly conserved regulators of membrane dynamics and protein trafficking. The interactions of large ARF GEFs with cellular membranes for localization and/or activation are likely to participate in regulated recruitment of ARF and effectors. However, these interactions remain largely unknown.

Research paper thumbnail of The Arf activator Gea2p and the P-type ATPase Drs2p interact at the Golgi in Saccharomyces cerevisiae

Journal of Cell Science, 2004

Research paper thumbnail of Ftx is a non-coding RNA which affects Xist expression and chromatin structure within the X-inactivation center region

Human Molecular Genetics, 2011

X chromosome inactivation (XCI) is an essential epigenetic process which involves several non-cod... more X chromosome inactivation (XCI) is an essential epigenetic process which involves several non-coding RNAs (ncRNAs), including Xist, the master regulator of X-inactivation initiation. Xist is flanked in its 5' region by a large heterochromatic hotspot, which contains several transcription units including a gene of unknown function, Ftx (five prime to Xist). In this article, we describe the characterization and functional analysis of murine Ftx. We present evidence that Ftx produces a conserved functional long ncRNA, and additionally hosts microRNAs (miR) in its introns. Strikingly, Ftx partially escapes X-inactivation and is upregulated specifically in female ES cells at the onset of X-inactivation, an expression profile which closely follows that of Xist. We generated Ftx null ES cells to address the function of this gene. In these cells, only local changes in chromatin marks are detected within the hotspot, indicating that Ftx is not involved in the global maintenance of the heterochromatic structure of this region. The Ftx mutation, however, results in widespread alteration of transcript levels within the X-inactivation center (Xic) and particularly important decreases in Xist RNA levels, which were correlated with increased DNA methylation at the Xist CpG island. Altogether our results indicate that Ftx is a positive regulator of Xist and lead us to propose that Ftx is a novel ncRNA involved in XCI.

Research paper thumbnail of Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin

Genome Research, 2011

The mammalian genome contains numerous regions known as facultative heterochromatin, which contri... more The mammalian genome contains numerous regions known as facultative heterochromatin, which contribute to transcriptional silencing during development and cell differentiation. We have analyzed the pattern of histone modifications associated with facultative heterochromatin within the mouse imprinted Snurf-Snrpn cluster, which is homologous to the human Prader-Willi syndrome genomic region. We show here that the maternally inherited Snurf-Snrpn 3-Mb region, which is silenced by a potent transcription repressive mechanism, is uniformly enriched in histone methylation marks usually found in constitutive heterochromatin, such as H4K20me3, H3K9me3, and H3K79me3. Strikingly, we found that trimethylated histone H3 at lysine 36 (H3K36me3), which was previously identified as a hallmark of actively transcribed regions, is deposited onto the silenced, maternally contributed 3-Mb imprinted region. We show that H3K36me3 deposition within this large heterochromatin domain does not correlate with transcription events, suggesting the existence of an alternative pathway for the deposition of this histone modification. In addition, we demonstrate that H3K36me3 is markedly enriched at the level of pericentromeric heterochromatin in mouse embryonic stem cells and fibroblasts. This result indicates that H3K36me3 is associated with both facultative and constitutive heterochromatin. Our data suggest that H3K36me3 function is not restricted to actively transcribed regions only and may contribute to the composition of heterochromatin, in combination with other histone modifications.

Research paper thumbnail of A role for non-coding Tsix transcription in partitioning chromatin domains within the mouse X-inactivation centre

Epigenetics & Chromatin, 2009

Background: Delimiting distinct chromatin domains is essential for temporal and spatial regulatio... more Background: Delimiting distinct chromatin domains is essential for temporal and spatial regulation of gene expression. Within the X-inactivation centre region (Xic), the Xist locus, which triggers X-inactivation, is juxtaposed to a large domain of H3K27 trimethylation (H3K27me3).