Gene environment directing regulation of gene expression

Samenvatting

Genomic rearrangements are often causal to malignant transformation. Rearrangements can disrupt a tumor-suppressor gene or generate an oncogene by gene fusion. However, many rearrangements have been found in non-coding regions, excluding that they contribute to oncogenic transformation through the disruption or creation of proteins. Since gene expression can be influenced by the gene environment, it is likely that rearrangements in non-coding regions cause transcriptional aberrations and thereby contribute to malignant transformation. In this project I therefore aim to elucidate how gene environment and genomic interaction domains influence the regulation of gene expression by:
- determining how the formation of interaction domains is influenced by genomic rearrangements, by performing Chromosome Conformation Capture analyses after creating rearrangements at a single model locus as well as genome-wide.
- analyzing how induced transcriptional activity affects the activity of neighboring genes, and if this depends on the boundaries of interaction domains, by allele-specific expression analysis after induced transcriptional activity at the model locus as well as in a high-throughput genome-wide manner.
Altogether this project will elucidate how gene environment influences transcriptional regulation. These findings will be instrumental to understand how translocations in non-coding regions can lead to malignant transformation.

Producten

Wetenschappelijk artikel

  • J.G. van Bemmel, H Mira-Bontenbal, J Gribnau(2015): Cis- and trans-regulation in X inactivation Chromosoma pp. NA - NA

Publieksinformatie

  • J.G. van Bemmel(2014): The Role of Chromatin Conformation in X-Chromosome Inactivation (XCI)
  • J.G. van Bemmel, J Gribnau, E Heard(2014): The role of TADs & regulatory domains in the regulation of X-chromosome inactivation
  • J.G. van Bemmel, J Gribnau, E Heard(2014): The role of TADs & regulatory domains in the regulation of X-chromosome inactivation
  • R Galupa, J.G. van Bemmel, C Picard, E Heard(2015): The structural and regulatory puzzle of the X-inactivation centre

Kenmerken

Projectnummer

825.13.002

Hoofdaanvrager

Dr. J.G. van Bemmel

Verbonden aan

Institut Curie, Heard Laboratory UMR3215

Uitvoerders

Dr. J.G. van Bemmel

Looptijd

01/11/2013 tot 21/03/2016