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Chromatin loops and causality loops: the influence of RNA upon spatial nuclear architecture

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Abstract

An intrinsic and essential trait exhibited by cells is the properly coordinated and integrated regulation of an astoundingly large number of simultaneous molecular decisions and reactions to maintain biochemical homeostasis. This is especially true inside the cell nucleus, where the recognition of DNA and RNA by a vast range of nucleic acid-interacting proteins organizes gene expression patterns. However, this dynamic system is not regulated by simple “on” or “off” signals. Instead, transcription factor and RNA polymerase recruitment to DNA are influenced by the local chromatin and epigenetic environment, a gene’s relative position within the nucleus and the action of noncoding RNAs. In addition, major phase-separated structural features of the nucleus, such as nucleoli and paraspeckles, assemble in direct response to specific transcriptional activities and, in turn, influence global genomic function. Currently, the interpretation of these data is trapped in a causality dilemma reminiscent of the “chicken and the egg” paradox as it is unclear whether changes in nuclear architecture promote RNA function or vice versa. Here, we review recent advances that suggest a complex and interdependent interaction network between gene expression, chromatin topology, and noncoding RNA function. We also discuss the functional links between these essential nuclear processes from the nanoscale (gene looping) to the macroscale (sub-nuclear gene positioning and nuclear body function) and briefly highlight some of the challenges that researchers may encounter when studying these phenomena.

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Acknowledgments

We are grateful to Rosalind Franklin University of Medicine and Science for their support of our work. We are also thankful to Dr. Karen Meaburn for her constructive comments during the writing of this review and Dr. Sergei Shevtsov for technical support during confocal microscopy. Finally, we sincerely apologize to those authors whose works on this large and fascinating topic were omitted from this manuscript due to space limitations.

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  1. Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, 60064, USA

    Iain A. Sawyer & Miroslav Dundr

  2. Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Iain A. Sawyer

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  1. Iain A. Sawyer
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  2. Miroslav Dundr
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Correspondence to Miroslav Dundr.

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This work was supported by NIH grant R01 GM 090156 from NIGMS (awarded to MD).

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Sawyer, I.A., Dundr, M. Chromatin loops and causality loops: the influence of RNA upon spatial nuclear architecture. Chromosoma 126, 541–557 (2017). https://doi.org/10.1007/s00412-017-0632-y

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