The role of imprinting in embryonic development and tumorigenesis

Imprinting is a mammalian adaptation that results in the mono-allelic expression of a subset of genes depending on their parental origin. It is believed that DNA methylation marks are responsible for maintaining imprinted gene expression patterns. The 'parental conflict' hypothesis was proposed to explain the evolution of imprinting and is based on the assumption that mammals arose from an ancestor that was polyandrous (multiple fathers within one litter). According to this hypothesis, conflict between the male and female over the allocation of maternal resources to the offspring led to the evolution of imprinting. Consistent with this, many imprinted genes are involved in embryonic or placental growth by regulating mitogenic pathways or the cell cycle. Loss of imprinting (LOI) has been found at specific loci in cancers, raising the possibility that altered expression of imprinted genes may also contribute to tumorigenesis. To investigate the effect of global LOI on embryonic development and cancer formation, imprint free (IF) embryonic stem (ES) cells were generated using conditional inactivation/reactivation of the DNA methyltransferase Dnmtl. Tetraploid complementation and chimera experiments revealed that IF-embryos fail to develop beyond E11.5 and display an overgrowth phenotype.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Holm, Teresa M

Advisor dc:contributor.advisor

• Rudolph Jaenisch.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/34187
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/34187

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/34187