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Expanding the roles of chromatin insulators in nuclear architecture, chromatin organization and genome function

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Abstract

Of the numerous classes of elements involved in modulating eukaryotic chromosome structure and function, chromatin insulators arguably remain the most poorly understood in their contribution to these processes in vivo. Indeed, our view of chromatin insulators has evolved dramatically since their chromatin boundary and enhancer blocking properties were elucidated roughly a quarter of a century ago as a result of recent genome-wide, high-throughput methods better suited to probing the role of these elements in their native genomic contexts. The overall theme that has emerged from these studies is that chromatin insulators function as general facilitators of higher-order chromatin loop structures that exert both physical and functional constraints on the genome. In this review, we summarize the result of recent work that supports this idea as well as a number of other studies linking these elements to a diverse array of nuclear processes, suggesting that chromatin insulators exert master control over genome organization and behavior.

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Abbreviations

NAPs:

Nucleoid associated proteins

BTB:

Bric-a-Brac/Tramtrack/Broad Complex

CTCF:

CCCTC-binding factor protein

BEAF-32:

Boundary element-associated factor of 32kD

Su(Hw):

Suppressor of Hairy wing

CP190:

Centrosomal Protein 190kD

Mod(mdg4)67.2:

Modifier of mdg4

GAF:

GAGA Factor

Dwg/Zw5:

Deformed wings

HSV-1:

Herpes simplex virus 1

EBV:

Epstein–Barr virus

KSHV:

Kaposi’s sarcoma-associated herpesvirus

SINE:

Short Interspersed Element

AS1/AS2:

Asymmetric leaves 1 and 2

L(3)mbt:

Lethal(3) malignant brain tumor

TADs:

Topologically associating domains

ESCs:

Embryonic stem cells

NPCs:

Neural progenitor cells

LCR:

Locus control regions

PRE:

Polycomb Response Element

eve:

Even skipped

ORC:

Origin recognition complex proteins

pre-RC:

Pre-replication complex

SBS:

Su(Hw) binding site

PARylation:

Poly (ADP-ribosyl)ation

PARP:

Poly (ADP-ribose) polymerase

SUMO:

Small ubiquitin-like modifier

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Acknowledgments

We would like to thank the current and former members of the Labrador Lab, including Hyuck-Joon Kang, Heather Wallace, Shaofei Zhang, Srilalitha Kuruganti, Maria P. Plata, Shih-Jui Hsu, Ran An, Ryan Rickels and Josh Barrios for collaboration and discussion. Work in the Labrador Lab was supported by Grants NIH GM78132-2 and NSF MCB-0616081 plus additional support from the College of Arts and Sciences, the Department of Biochemistry and Cellular and Molecular Biology and the Office of Research at the University of Tennessee, Knoxville. TS was supported by a Graduate Research Fellowship from the National Science Foundation.

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  1. Todd Schoborg

    Present address: Laboratory of Molecular Machines and Tissue Architecture, Cell Biology and Physiology Center, National Heart, Lung and Blood Institute, National Institutes of Health, 50 South Dr Rm 2122, Bethesda, MD, 20892, USA

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  1. Department of Biochemistry, Cellular and Molecular Biology, The University of Tennessee, M407 Walters Life Sciences, 1414 Cumberland Avenue, Knoxville, TN, 37996, USA

    Todd Schoborg & Mariano Labrador

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  2. Mariano Labrador
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Correspondence to Todd Schoborg or Mariano Labrador.

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Schoborg, T., Labrador, M. Expanding the roles of chromatin insulators in nuclear architecture, chromatin organization and genome function. Cell. Mol. Life Sci. 71, 4089–4113 (2014). https://doi.org/10.1007/s00018-014-1672-6

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  • DOI: https://doi.org/10.1007/s00018-014-1672-6

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