Abstract
The promoters of mammalian genes are commonly regulated by multiple distal enhancers, which physically interact within discrete chromatin domains. How such domains form and how the regulatory elements within them interact in single cells is not understood. To address this we developed Tri-C, a new Chromosome Conformation Capture (3C) approach to identify concurrent chromatin interactions at individual alleles. Analysis by Tri-C reveals heterogeneous patterns of single-allele interactions between CTCF boundary elements, indicating that the formation of chromatin domains likely results from a dynamic process. Within these domains, we observe specific higher-order structures involving simultaneous interactions between multiple enhancers and promoters. Such regulatory hubs provide a structural basis for understanding how multiple cis-regulatory elements act together to establish robust regulation of gene expression.
Highlights
Precise spatial and temporal patterns of gene expression during development and differentiation are controlled by cis-regulatory elements including promoters, enhancers and boundary elements
The flanking CTCF-binding elements do not participate in these enhancer-promoter interactions, but form diffuse interactions with the chromatin bound by CTCF on either side of the domain, spanning contiguous regions of ~50 kb
We show that high-resolution singleallele chromatin structures do not support a model of stable loops forming between individual CTCF-binding sites, but indicate a dynamic mechanism such as loop extrusion underlying the formation of chromatin domains
Summary
Precise spatial and temporal patterns of gene expression during development and differentiation are controlled by cis-regulatory elements including promoters, enhancers and boundary elements. The interaction and activity of these elements depend on and influence their structural organization within the nucleus. We have previously shown that the active mouse α-globin cluster and its regulatory elements are located in a decompacted ~70 kb chromatin domain that forms early in erythroid differentiation and is flanked by CTCFbinding sites–. Within this domain, the α-globin genes interact with five enhancer elements, which cooperate in an additive manner to upregulate gene expression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
