Animation

Dynamic Control of Nuclear Receptor Transcription

Animation: Nuclear Receptor and Transcriptional

Complex Cycles

Amy M. Fowler and Elaine T. Alarid*

Department of Physiology, University of Wisconsin-Madison, 1300 University Avenue, Madison, WI 53706, USA.

Animation. Nuclear receptors are intracellular transcriptional regulators that reside in either the cytoplasm or nucleus in the inactive state. Based on experiments following the dynamics of the glucocorticoid receptor and estrogen receptor (1, 2), this animation shows nuclear estrogen receptor (ER) and its interaction with a short two-nucleosome fragment of chromatin in the absence and presence of estrogen. Gene activation appears to involve cyclical assembly and disassembly of protein complexes on the promoter region of the gene to be expressed. The periodic associations of different combinations of multimolecular complexes on the DNA over time highlight the dynamics underlying transcriptional regulation.

In this animation, the events that occur on the DNA are represented by the ordered recruitment of protein components to a larger macromolecular complex. The names and abbreviations of the various proteins are listed in Table 1, and their sizes in the animation are depicted in proportion to their relative molecular weights. Classes of proteins, such as HATs and HMTs, are maintained in a single color, and switching among individual proteins that belong to the same class is shown by a change in size and shape. Chromatin remodeling is indicated by an alteration in how tightly the DNA is associated with the histones. Posttranslational modification of histones and phosphorylation of RNAPII are indicated by color changes.

Table 1. Proteins involved in the nuclear receptor-chromatin cycles. Not all proteins are shown individually in the animation. Bold entries indicate the general name given for either a multiprotein complex or a class of proteins.

Abbreviation Name
ER Estrogen Receptor
hSWI/SNF



hBRG1

INI1

hBRM1
ATP-dependent chromatin remodeling complex (shown as SWI/SNF in the animation)

Brahma-related gene 1 protein

Integrase interactor 1

Brahma protein
HAT

p300

GCN5

Tip60

pCAF

CBP
Histone acetyltransferase

p300

General control positive factor

Tat-interacting protein

p300/CBP associated factor

CREB binding protein
HMT

PRMT1

CARM1

Histone methyltransferase

Protein arginine methyltransferase

Cofactor associated arginine methyltransferase
CoA

SRC1

SRC3
Coactivator

Steroid receptor coactivator 1

Steroid receptor coactivator 3
TAFII

TAFII250

TAFII130
TATA binding protein (TBP)-associated factor

TBP-associated factor of 250 kD

TBP-associated factor of 130 kD
TBP

TATA box-binding protein
TFIIA Component of the basal transcription machinery included in RNA polymerase II holoenzyme
RNAPII RNA polymerase II
E3 ligase

E6AP

MDM2
E3 ubiquitin ligase (shown as E3 in the animation)

Oncoprotein E6-associated protein

Murine double minute 2
Mediator

Med7

TRAP220
(multiprotein complex)

Mediator subunit 7

Thyroid hormone receptor-associated protein of 220 kD
CDK7 Cyclin-dependent kinase 7

(subunit of TFIIH)
Elongator

Elp1

Elp3
(multiprotein complex)

Elongator protein 1

Elongator protein 3
APIS



SUG1
AAA ATPase proteins independent of 20S

(19S regulatory component of the proteasome)

Suppressor gene 1
HDAC

HDAC1

HDAC7
Histone deacetylase

Histone deacetylase 1

Histone deacetylase 7
HSP70 Heat shock protein of 70 kD
NuRD Nucleosome remodeling and histone deactylation (multiprotein complex, 15 subunits)

Two versions of the animation are available: A smaller size file, which is 2,203 kb and opens in a smaller window, or a larger version, which is 7,686 kb and opens in a larger window. Both animations show the same nuclear receptor cycle. Press the start button at the bottom of the QuickTime movie player to start the animation. Press the pause and play button to start and stop the action at any point.

[Access Small Animation] [Access Large Animation]

Technical Details

Format: Quicktime file (mov file)

Size: 2,203 kb (small version) or 7,686 kb (large version)

Requirements: This animation will play with Quicktime (http://www.apple.com/quicktime/download/).

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Corresponding author. E-mail, //alarid{at}physiology.wisc.edu

References

    • R. Métivier, G. Penot, M. R. Hübner, G. Reid, H. Brand, M. Koš, F. Gannon, Estrogen receptor-a directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115, 751-763 (2003).
    • A. K. Nagaich, D. A. Walker, R. Wolford, G. L. Hager, Rapid periodic binding and displacement of the glucocorticoid receptor during chromatin remodeling. Mol. Cell 14, 163-174 (2004).

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      Citation: A. M. Fowler, E. T. Alarid, Dynamic control of nuclear receptor transcription. Sci. STKE2004, pe51 (2004).

      © 2004 American Association for the Advancement of Science