Chromosomal Contact Permits Transcription between Coregulated Genes

Transcription of coregulated genes occurs in the context of long-range chromosomal contacts that form multigene complexes. Such contacts and transcription are lost in knockout studies of transcription factors and structural chromatin proteins. To ask whether chromosomal contacts are required for cot...

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Bibliographic Details
Published in:Cell 2013-10, Vol.155 (3), p.606-620
Main Authors: Fanucchi, Stephanie, Shibayama, Youtaro, Burd, Shaun, Weinberg, Marc S., Mhlanga, Musa M.
Format: Article
Language:English
Subjects:
Chromosomes - chemistry
Deoxyribonucleases - metabolism
Gene Expression Regulation
Genetic Techniques
Human Umbilical Vein Endothelial Cells
Humans
In Situ Hybridization, Fluorescence
Repressor Proteins - genetics
Single-Cell Analysis
Transcription, Genetic
Tumor Necrosis Factor-alpha - metabolism
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Summary:Transcription of coregulated genes occurs in the context of long-range chromosomal contacts that form multigene complexes. Such contacts and transcription are lost in knockout studies of transcription factors and structural chromatin proteins. To ask whether chromosomal contacts are required for cotranscription in multigene complexes, we devised a strategy using TALENs to cleave and disrupt gene loops in a well-characterized multigene complex. Monitoring this disruption using RNA FISH and immunofluorescence microscopy revealed that perturbing the site of contact had a direct effect on transcription of other interacting genes. Unexpectedly, this effect on cotranscription was hierarchical, with dominant and subordinate members of the multigene complex engaged in both intra- and interchromosomal contact. This observation reveals the profound influence of these chromosomal contacts on the transcription of coregulated genes in a multigene complex. [Display omitted] •Transcription of genes in a multigene complex can be asymmetric•Site-specific nucleases can discretely disrupt chromatin loops•Disrupting chromatin contacts influences cotranscription of interacting genes•Chromatin looping in multigene complexes may be governed by hierarchical regulation Transcription of coregulated genes occurs in the context of long-range chromosomal contacts that form multigene complexes. Disruption of the contacts shows that they are necessary for transcription and that not all genes have equal impact on the transcription of the others but, rather, exhibit a hierarchy of influence.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2013.09.051