Noncoding RNAs and Chromatin Modifications in the Developmental Control of Imprinted Genes

摘要

In mammals, hundreds of protein-coding genes and regulatory noncoding RNAs (ncRNAs) are controlled by the epigenetic phenomenon of genomic imprinting. These unusual genes are organized in clusters in the genome, and their mono-allelic expression depends on whether the allele is inherited from the mother or from the father. The imprinted gene expression is mediated by essential regulatory sequence elements called "imprinting control regions" (ICRs), which carry mono-allelic DNA methylation marks. These germ line-derived imprints are maintained throughout development and after birth, a process which is linked consistently to specific chromatin modifications. The way ICRs mediate mono-allelic gene expression is tissue specific at many of the imprinted gene clusters. At several imprinted gene domains, the ICR expresses a long ncRNA that mediates chromatin repression in cis. At other imprinted domains, the ICR differentially structures higher-order chromatin that allows, or prevents, transcription of close-by genes. Here, I introduce the epigenetic phenomenon of genomic imprinting and discuss how long ncRNAs and chromatin contribute to its developmental regulation.