Publications by authors named "Maud Bizot"

Methylation and demethylation of cytosines in DNA are believed to act as keystones of cell-specific gene expression by controlling the chromatin structure and accessibility to transcription factors. Cancer cells have their own transcriptional programs, and we sought to alter such a cancer-specific program by enforcing expression of the catalytic domain (CD) of the methylcytosine dioxygenase TET2 in breast cancer cells. The TET2 CD decreased the tumorigenic potential of cancer cells through both activation and repression of a repertoire of genes that, interestingly, differed in part from the one observed upon treatment with the hypomethylating agent decitabine.

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Article Synopsis
  • Cell identity is shaped by how genetics and epigenetics work together to control gene activity.
  • A specific change in DNA, where a part called 5-methylcytosine transforms into 5-hydroxymethylcytosine, helps to manage the identity of cells, especially in diseases like multiple myeloma (MM).
  • Researchers found a special signature in MM that linked to a gene called FAM72D, showing that it could predict poor outcomes for patients, especially since it’s part of a network that affects how fast cells grow and survive.
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Epigenetic mechanisms are believed to play key roles in the establishment of cell-specific transcription programs. Accordingly, the modified bases 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been observed in DNA of genomic regulatory regions such as enhancers, and oxidation of 5mC into 5hmC by Ten-eleven translocation (TET) proteins correlates with enhancer activation. However, the functional relationship between cytosine modifications and the chromatin architecture of enhancers remains elusive.

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Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII/NR2F2) is an orphan member of the nuclear receptor family of transcription factors whose activities are modulated upon binding of small molecules into an hydrophobic ligand-binding pocket (LBP). Although the LBP of COUP-TFII is filled with aromatic amino-acid side chains, alternative modes of ligand binding could potentially lead to regulation of the orphan receptor. Here, we screened a synthetic and natural compound library in a yeast one-hybrid assay and identified 4-methoxynaphthol as an inhibitor of COUP-TFII.

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Human Hereditary Sensory Autonomic Neuropathies (HSANs) are characterized by insensitivity to pain, sometimes combined with self-mutilation. Strikingly, several sporting dog breeds are particularly affected by such neuropathies. Clinical signs appear in young puppies and consist of acral analgesia, with or without sudden intense licking, biting and severe self-mutilation of the feet, whereas proprioception, motor abilities and spinal reflexes remain intact.

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Article Synopsis
  • Estradiol signaling helps understand how DNA sequences, chromatin modifications, and genome organization work together to regulate gene expression, particularly through estrogen receptors (ER).
  • The study focused on a specific 2-Mb region containing estrogen-sensitive genes in breast cancer cells, highlighting how hormone presence and cohesin proteins affect the 3D structure of DNA to facilitate gene regulation.
  • Using advanced techniques, the researchers identified specific ER binding sites (ERBSs) that connect to gene regulation, providing insights into how enhancers work together and the potential redundancy in ERBS functions.
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  • Enhancers are regions that help regulate gene expression and can change during cell development, influenced by modifications in histones and DNA.
  • This study found that a new DNA modification called 5-hydroxymethylcytosine (5hmC) is linked to transcription factor activity in specific cell types during their differentiation process, like neural cells and fat cells.
  • The research suggests that gaining 5hmC in certain regions of DNA is a key step towards activating enhancers that regulate genes important for specific tissues, indicating that this modification plays a vital role in determining cell identities.
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Transcription factors (TFs) bind specifically to discrete regions of mammalian genomes called cis-regulatory elements. Among those are enhancers, which play key roles in regulation of gene expression during development and differentiation. Despite the recognized central regulatory role exerted by chromatin in control of TF functions, much remains to be learned regarding the chromatin structure of enhancers and how it is established.

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