Autosomal random asynchronous replication is analogous to X-chromosome inactivation

A number of mammalian genes are expressed from only one of two alleles in either an imprinted or random manner. Those belonging to the random class include X-linked genes subject to X inactivation, as well as a number of autosomal genes, including odorant receptors, immunoglobulins, T-cell receptors, interleukins, natural killer-cell receptors, and pheromone receptors. Random asynchronous replication of DNA in S-phase represents an epigenetic mark that often parallels monoallelic expression. All randomly monoallelically expressed genes discovered to date replicate asynchronously in S-phase, though not all of the genes contained within asynchronous domains are monoallelically expressed. The focus of my work has been on understanding this random choice that cells make between two sequence-identical alleles. Using two-color fluorescent in situ hybridization (FISH) analyses, the random asynchronous replication of a large number of human and mouse genes appears to be coordinated at the level of entire chromosomes. This regulatory scheme is reminiscent of random X-chromosome inactivation, the dosage compensation machinery in mammals. We have shown that autosomal coordination responds to trisomy in a fashion similar to X inactivation, with one copy of the trisomic chromosome marked for early replication and the other two rendered late replicating.

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

• Ensminger, Alexander Wilson

Advisor dc:contributor.advisor

• Andrew Chess.

• 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/1721.1/34197
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/34197

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/34197