Importance Of Histone Variant H2AZ Acetylation In Gene Activation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$611,737.00
Summary
DNA is packaged in the cell in such a way that essential genes are available to be switched on by the transcription machinery. The packaging involves nucleosomes, that consist of four histone proteins, H2A, H2B, H3 and H4. H2A.Z is a histone variant that is often over expressed in cancer, and therefore could lead to abnormal gene transcription. This project is focused on understanding the role of H2A.Z in gene deregulation in cancer as modification of this mark may provide a potential novel canc ....DNA is packaged in the cell in such a way that essential genes are available to be switched on by the transcription machinery. The packaging involves nucleosomes, that consist of four histone proteins, H2A, H2B, H3 and H4. H2A.Z is a histone variant that is often over expressed in cancer, and therefore could lead to abnormal gene transcription. This project is focused on understanding the role of H2A.Z in gene deregulation in cancer as modification of this mark may provide a potential novel cancer therapeutic target.Read moreRead less
Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably e ....Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably extend the information potential of the genetic code. In addition, it is now established that chromatin structural features can influence gene expression. In vitro studies support a model in which chromatin functions as a barrier for the access to DNA. Therefore this organization has to be tighly regulated and dynamic to allow the protein-DNA interactions critical for nuclear functions. Importantly genome organisation provides in addition to genetic information another layer of information, so called epigenetic, which by definition means that it is stably inherited throughout cellular divisions, yet it is not encoded genetically. Thus each cell type will display a specific epigenome. We have recently constructed small human minichromosomes, which are much easier to study than the much larger normal chromosomes. The present project proposes to define the epigenetic feature across an entire human chromosome using our minichhromosomes as working models. The outcome will be a significant gain in our knowledge on the processes underlying epigenetic regulation, the organisation of specialised chromatin domain, and behaviour of the chromosomes.Read moreRead less