CRISPR-Mediated Reorganization of Chromatin Loop Structure

Citations Over Time

Abstract

Recent studies have clearly shown that long-range, three-dimensional chromatin looping interactions play a significant role in the regulation of gene expression, but whether looping is responsible for or a result of alterations in gene expression is still unknown. Until recently, how chromatin looping affects the regulation of gene activity and cellular function has been relatively ambiguous, and limitations in existing methods to manipulate these structures prevented in-depth exploration of these interactions. To resolve this uncertainty, we engineered a method for selective and reversible chromatin loop re-organization using CRISPR-dCas9 (CLOuD9). The dynamism of the CLOuD9 system has been demonstrated by successful localization of CLOuD9 constructs to target genomic loci to modulate local chromatin conformation. Importantly, the ability to reverse the induced contact and restore the endogenous chromatin conformation has also been confirmed. Modulation of gene expression with this method establishes the capacity to regulate cellular gene expression and underscores the great potential for applications of this technology in creating stable de novo chromatin loops that markedly affect gene expression in the contexts of cancer and development.

Related Papers

• → Mechanisms and Functions of ATP-Dependent Chromatin-Remodeling Enzymes(2013)655 cited
• → Chromatin remodeling by nuclear receptors(2003)105 cited
• → The ISWI and CHD1 chromatin remodelling activities influence ADH2 expression and chromatin organization(2006)33 cited
• → In Vitro Studies of Nucleosome Positioning and Stability at the PHO5 and PHO8 Promoters in Saccharomyces cerevisiae(2006)
• → Chromatin Modification and Remodeling in Heart Development(2010)