title: Transcriptional effects of gene dose reduction.
abstract: Large-scale gene dose reductions usually lead to abnormal phenotypes or death. However, male mammals, Drosophila, and Caenorhabditis elegans have only one X chromosome and thus can be considered as monosomic for a major chromosome. Despite the deleterious effects brought about by such gene dose reduction in the case of an autosome, X chromosome monosomy in males is natural and innocuous. This is because of the nearly full transcriptional compensation for X chromosome genes in males, as opposed to no or partial transcriptional compensation for autosomal one-dose genes arising due to deletions. Buffering, the passive absorption of disturbance due to enzyme kinetics, and feedback responses triggered by expression change contribute to partial compensation. Feed-forward mechanisms, which are active responses to genes being located on the X, rather than actual gene dose are important contributors to full X chromosome compensation. In the last decade, high-throughput techniques have provided us with the tools to effectively and quantitatively measure the small-fold transcriptional effects of dose reduction. This is leading to a better understanding of compensatory mechanisms.
authors.affiliation: Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-8028, USA. zhen-xia.chen@nih.gov.
authors.forename: Zhen-Xia
authors.initials: ZX
authors.lastname: Chen
authors.forename: Kseniya
authors.initials: K
authors.lastname: Golovnina
authors.forename: Hina
authors.initials: H
authors.lastname: Sultana
authors.forename: Satish
authors.initials: S
authors.lastname: Kumar
authors.forename: Brian
authors.initials: B
authors.lastname: Oliver