The Human Imprintome: Regulatory Mechanisms, Methods of Ascertainment, and Roles in Disease Susceptibility

Abstract

Imprinted genes form a special subset of the genome, exhibiting monoallelic expression in a parent-of-origin–dependent fashion. This monoallelic expression is controlled by parental-specific epigenetic marks, which are established in gametogenesis and early embryonic development and are persistent in all somatic cells throughout life. We define this specific set of cis-acting epigenetic regulatory elements as the imprintome, a distinct and specially tasked subset of the epigenome. Imprintome elements contain DNA methylation and histone modifications that regulate monoallelic expression by affecting promoter accessibility, chromatin structure, and chromatin configuration. Understanding their regulation is critical because a significant proportion of human imprinted genes are implicated in complex diseases. Significant species variation in the repertoire of imprinted genes and their epigenetic regulation, however, will not allow model organisms solely to be used for this crucial purpose. Ultimately, only the human will suffice to accurately define the human imprintome.

Aberrant allele-switch imprinting of a novel IGF1R intragenic antisense non-coding RNA in breast cancers

“…3C), in agreement with the data in haematopoietic malignancies [26]. Together, our data validate IRAIN as a new member of the family of imprinted genes [41].…”

The landscape of genomic imprinting across diverse adult human tissues

“…S20), which is consistent with imprinted genes often being growth regulators (Skaar et al 2012;Lawson et al 2013). Without dosage compensation, silencing of one allele via imprinting should halve expression levels (Susiarjo et al 2013).…”

“…S6; Skaar et al 2012;Court et al 2014). Analysis of the methylation array data in the GenCord data set showed that imprinted genes had a Figure 2.…”

“…It plays a role in several Mendelian diseases and there is growing evidence for its role in common diseases as well as cancer. It is a dynamic mechanism with varying degrees of monoallelic expression between tissues and developmental stages (Wolf et al 2008;Kong et al 2009;Skaar et al 2012;Lawson et al 2013;Peters 2014). While previous studies have catalogued imprinted genes and shed light on patterns and mechanisms of imprinting, these data are derived from heterogeneous sources, often covering only specific loci, tissues, and developmental stages, especially in humans.…”

A New Case of a Rare Combination of Temple Syndrome and Mosaic Trisomy 14 and a Literature Review

“…Although the CTCFL gene is not directly associated with any genetic disorder, it is believed to participate in some epigenetic mechanisms. Since the CTCFL gene has been found to be associated with the regulation of several imprinting control regions [Skaar et al, 2012] and the patient has growth retardation and body asymmetry typical for many imprinting disorders, an analysis of imprinted regions in chromosomes 6, 7, and 14 was additionally performed.…”