Modulation of chromosome function by chromatin remodeling agents
OwnerUlrich Laemmliinventor
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Abstract
The present invention concerns a process for modulating the function of a DNA element in a eukaryotic cell, comprising the step of contacting a genomic DNA element, so-called “chromatin responsive element” (CRE), with a compound having a molecular weight of less than approximately 5 KDa, and having the capacity to bind in a_sequence-specific manner to said CRE, said step of contacting being carried out in conditions permitting chromatin remodeling of the CRE by said compound, wherein said chromatin remodeling of the CRE alters the activity of one or more other DNA elements, so called “modulated DNA elements” in the genome.
Claims76
Process for modulating the function of a DNA element in a eukaryotic cell,
- comprising the step of contacting a genomic DNA element, so-called “chromatin responsive element” (CRE),
- with a compound having a molecular weight of less than approximately 5 KDa, and having the capacity to bind in a_sequence-specific manner to said CRE,
- said step of contacting being carried out in conditions permitting chromatin remodeling of the CRE by said compound,
- wherein said chromatin remodeling of the CRE alters the activity of one or more other DNA elements, so called “modulated DNA elements” in the genome.
Process for modulating the epigenetic state of a heterologous gene in a cell, said process comprising the steps of:
- transforming said cell with a nucleic acid sequence comprising said heterologous gene, and with a nucleic acid sequence comprising a so-called heterologous “chromatin responsive element” (CRE),
- introducing into said cell a compound which has the capacity to bind in a sequence-specific manner to said heterologous CRE,
- said step of contacting being carried out in conditions permitting chromatin remodeling of the heterologous CRE by said compound,
- wherein said chromatin modelling of the CRE modulates the epigenetic state of the heterologous gene.
Gene expression kit suitable for modulating the epigenetic state of a heterologous gene in a cell, said kit comprising
- a nucleic acid molecule comprising said heterologous gene
- a nucleic acid molecule comprising a so-called heterologous “CRE”, said heterologous CRE being a sequence whose chromatin status allows the modulation of chromosome function in cis or trans;
- a compound having a molecular weight of less than approximately 5 KDa, and having the capacity to bind in a sequence-specific manner to said CRE.
Cell containing a compound having a molecular weight of less than 5 KDa, and having the capacity to bind in a sequence-specific manner to a genomic CRE, said CRE being a sequence whose chromatin status allows the modulation of chromosome function in cis or trans.
Compound having the capacity to bind, in a sequence-specific manner, to a predetermined CRE, said CRE being a sequence whose chromatin status allows modulation of chromosome function in cis or in trans, with the proviso that said compound is not distamycin, HMG-I/Y, or MATH20.
Compound having a molecular weight of less than 5 KDa and having the capacity to bind, in a sequence-specific manner, to a predetermined CRE, said CRE being a sequence whose chromatin status allows modulation of chromosome function in cis or in trans, said compound having the capacity to specifically recognise a sequence of at least 6 nucleotides.
Pharmaceutical composition comprising a compound having the capacity to bind, in a sequence-specific manner, to a predetermined CRE, said CRE being a sequence whose chromatin status allows modulation of chromosome function in cis or in trans, in association with a physiologically acceptable excipient, with the proviso that said compound is not distamycin, HMG-I/Y or MATH20.
Pharmaceutical composition comprising a compound having a molecular weight of less than 5 kDa, and having the capacity to bind, in a sequence-specific manner, to a predetermined CRE having at least 6 nucleotides, and said CRE being a DNA sequence whose chromatin status allows modulation of chromosome function in cis or in trans, in association with a physiologically acceptable excipient.
Association of pharmaceutical compositions, comprising a first pharmaceutical composition containing
- a nucleic acid molecule comprising a heterologous gene
- a nucleic acid molecule comprising a so-called heterologous “CRE”, said heterologous CRE being a sequence whose chromatin status allows the modulation of chromosome function in cis or trans, said nucleic acid molecules being in association with a physiologically acceptable excipient, and
- a second pharmaceutical composition comprising a compound having the capacity to bind, in a sequence-specific manner, to said CRE, in association with a physiologically acceptable excipient.
Composition comprising a compound having the capacity to bind, in a sequence-specific manner, to a predetermined CRE having at least 6 nucleotides, said CRE being a DNA sequence whose chromatin status allows modulation of gene function in cis or in trans, for use in therapy, with the proviso that said compound is not distamycin, HMG-I/Y, or MATH20.
Composition comprising a compound having a molecular weight of less than 5 kDa, and having the capacity to bind, in a sequence-specific manner, to a predetermined CRE having at least 6 nucleotides, said CRE being a DNA sequence whose chromatin status allows modulation of gene function in cis or in trans, for use in therapy.
DNA-binding compound capable of sequence specific binding to genomic DNA, said compound being an oligomer comprising cyclic heterocycles having at least one annular nitrogen, and optionally at least one aliphatic amino acid residue, wherein said compound is fluorescent or fluorescently labelled.
Method for identifying CREs in a genome, said method comprising:
- contacting genomic DNA containing a DNA element whose function is to be modulated, with a series of compounds having the capacity to bind in a sequence specific manner to DNA elements situated upstream, downstream or within the DNA element to be modulated,
- selection of those compounds capable of modulating the epigenetic state of the DNA element to be modulated, for example using chromatin probes such as nucleases.
Dependencies are inferred from the claim text.