Deciphering the code of silence: Mechanisms of gene repression with connections to human disease

Laura E. Norwood, Karrie A. Hines, Lori L. Wallrath

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations


Proper regulation of gene expression is required for normal growth and development. Developmental abnormalities and disease can result from the misregulation of gene expression. While some genes are controlled by mechanisms of activation, a significant proportion of genes are controlled by mechanisms of silencing. Silencing can account for the inactivation of the approximately 1000 genes on the human X-chromosome, for uniparental inactivation of chromosomal domains, and for inactivation of individual genes. Common features of silencing events include initiation by RNAs, either as noncoding RNAs expressed from a single gene, that remain associated near the site of synthesis, or as small interfering RNA molecules that act in trans. Other common epigenetic features include specific histone modifications, which generate a code for silent chromatin, and DNA methylation. Nonhistone chromosomal proteins have been discovered that associate with specific histone modifications. These nonhistone chromosomal proteins, "translators" of the histone code, include Heterochromatin Protein 1 and Polycomb, two factors that play a role in organizing chromatin structure. This review discusses discoveries made on gene silencing systems and their connections with disease.

Original languageEnglish (US)
Pages (from-to)308-324
Number of pages17
Issue number6
StatePublished - Jun 2004
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry
  • Molecular Biology


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