Chromatin remodeling and tissue-selective responses of nuclear hormone receptors

2002 ◽  
Vol 80 (3) ◽  
pp. 343-351 ◽  
Author(s):  
Pei-Wen Hsiao ◽  
Bonnie J Deroo ◽  
Trevor K Archer
Keyword(s):  
Chromatin Remodeling ◽  
Molecular Mechanisms ◽  
Hormone Receptors ◽  
Protein Complexes ◽  
Nuclear Hormone Receptor ◽  
Histone Acetyltransferases ◽  
Nuclear Hormone Receptors ◽  
Receptor Ligands ◽  
Eukaryotic Genes ◽  
Chromatin Remodeling Complexes

Chromatin structure of eukaryotic genes regulates gene expression by controlling the accessibility of regulatory factors. To overcome the inhibitory nature of chromatin, protein complexes that modify higher order chromatin organization and histone–DNA contacts are critical players in regulating transcription. For example, nuclear hormone receptors regulate transcription by interacting with ATP-dependent chromatin-remodeling complexes and coactivators, which include histone acetyltransferases and histone methylases that modify the basic residues of histones. A growing number of tissue-specific nuclear hormone receptor ligands, termed "selective modulators", owe their specificity, at least in part, to the differential recruitment of these chromatin-modifying coactivators. The molecular mechanisms by which these compounds modulate the functions of nuclear hormone receptors are discussed here.Key words: chromatin, BRG1, SWI–SNF, nuclear receptor, glucorticoid receptor, transcription, MMTV.

Nucleosome organization and targeting of SWI/SNF chromatin-remodeling complexes: contributions of the DNA sequenceThis paper is one of a selection of papers published in this Special Issue, entitled 28th International West Coast Chromatin and Chromosomes Conference, and has undergone the Journal's usual peer review process.

2007 ◽  
Vol 85 (4) ◽  
pp. 419-425 ◽  
Author(s):  
Martin Montecino ◽  
Janet L. Stein ◽  
Gary S. Stein ◽  
Jane B. Lian ◽  
Andre J. van Wijnen ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Peer Review Process ◽  
Gene Promoter ◽  
Limited Attention ◽  
Dependent Manner ◽  
Nucleosome Remodeling ◽  
Eukaryotic Genes

Chromatin organization within the nuclear compartment is a fundamental mechanism to regulate the expression of eukaryotic genes. During the last decade, a number of nuclear protein complexes with the ability to remodel chromatin and regulate gene transcription have been reported. Among these complexes is the SWI/SNF family, which alters chromatin structure in an ATP-dependent manner. A considerable effort has been made to understand the molecular mechanisms by which SWI/SNF catalyzes nucleosome remodeling. However, limited attention has been dedicated to studying the role of the DNA sequence in this remodeling process. Therefore, in this minireview, we discuss the contribution of nucleosome positioning and nucleosome excluding sequences to the targeting and activity of SWI/SNF complexes. This discussion includes results from our group using the rat osteocalcin gene promoter as a model. Based on these results, we postulate a model for chromatin remodeling and transcriptional activation of this gene in osteoblastic cells.

scholarly journals Small-Molecule Hormones: Molecular Mechanisms of Action

2013 ◽  
Vol 2013 ◽  
pp. 1-21 ◽  
Author(s):  
Monika Puzianowska-Kuznicka ◽  
Eliza Pawlik-Pachucka ◽  
Magdalena Owczarz ◽  
Monika Budzińska ◽  
Jacek Polosak
Keyword(s):  
Transcription Factors ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Hormone Receptors ◽  
Target Genes ◽  
Direct Interaction ◽  
Nuclear Hormone Receptors ◽  
Membrane Phospholipids ◽  
Basal Transcription Factors ◽  
Hormonal Stimulus

Small-molecule hormones play crucial roles in the development and in the maintenance of an adult mammalian organism. On the molecular level, they regulate a plethora of biological pathways. Part of their actions depends on their transcription-regulating properties, exerted by highly specific nuclear receptors which are hormone-dependent transcription factors. Nuclear hormone receptors interact with coactivators, corepressors, basal transcription factors, and other transcription factors in order to modulate the activity of target genes in a manner that is dependent on tissue, age and developmental and pathophysiological states. The biological effect of this mechanism becomes apparent not earlier than 30–60 minutes after hormonal stimulus. In addition, small-molecule hormones modify the function of the cell by a number of nongenomic mechanisms, involving interaction with proteins localized in the plasma membrane, in the cytoplasm, as well as with proteins localized in other cellular membranes and in nonnuclear cellular compartments. The identity of such proteins is still under investigation; however, it seems that extranuclear fractions of nuclear hormone receptors commonly serve this function. A direct interaction of small-molecule hormones with membrane phospholipids and with mRNA is also postulated. In these mechanisms, the reaction to hormonal stimulus appears within seconds or minutes.

scholarly journals Alien, a Highly Conserved Protein with Characteristics of a Corepressor for Members of the Nuclear Hormone Receptor Superfamily

1999 ◽  
Vol 19 (5) ◽  
pp. 3383-3394 ◽  
Author(s):  
Uwe Dressel ◽  
Dorit Thormeyer ◽  
Boran Altincicek ◽  
Achim Paululat ◽  
Martin Eggert ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Retinoic Acid Receptor ◽  
Specific Interaction ◽  
Gene Activation ◽  
Nuclear Hormone Receptor ◽  
Nuclear Hormone Receptors ◽  
Reporter Assays

ABSTRACT Some members of nuclear hormone receptors, such as the thyroid hormone receptor (TR), silence gene expression in the absence of the hormone. Corepressors, which bind to the receptor’s silencing domain, are involved in this repression. Hormone binding leads to dissociation of corepressors and binding of coactivators, which in turn mediate gene activation. Here, we describe the characteristics of Alien, a novel corepressor. Alien interacts with TR only in the absence of hormone. Addition of thyroid hormone leads to dissociation of Alien from the receptor, as shown by the yeast two-hybrid system, glutathioneS-transferase pull-down, and coimmunoprecipitation experiments. Reporter assays indicate that Alien increases receptor-mediated silencing and that it harbors an autonomous silencing function. Immune staining shows that Alien is localized in the cell nucleus. Alien is a highly conserved protein showing 90% identity between human and Drosophila. Drosophila Alien shows similar activities in that it interacts in a hormone-sensitive manner with TR and harbors an autonomous silencing function. Specific interaction of Alien is seen with Drosophila nuclear hormone receptors, such as the ecdysone receptor and Seven-up, the Drosophila homologue of COUP-TF1, but not with retinoic acid receptor, RXR/USP, DHR 3, DHR 38, DHR 78, or DHR 96. These properties, taken together, show that Alien has the characteristics of a corepressor. Thus, Alien represents a member of a novel class of corepressors specific for selected members of the nuclear hormone receptor superfamily.

The Drosophila trithorax group proteins BRM, ASH1 and ASH2 are subunits of distinct protein complexes

Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 3955-3966 ◽  
Author(s):  
O. Papoulas ◽  
S.J. Beek ◽  
S.L. Moseley ◽  
C.M. McCallum ◽  
M. Sarte ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Protein Complexes ◽  
Dominant Negative ◽  
Homeotic Genes ◽  
Atpase Subunit ◽  
Trithorax Group ◽  
Chromatin Remodeling Complexes ◽  
Trithorax Group Proteins ◽  
Drosophila Embryos

The trithorax group gene brahma (brm) encodes an activator of Drosophila homeotic genes that functions as the ATPase subunit of a large protein complex. To determine if BRM physically interacts with other trithorax group proteins, we purified the BRM complex from Drosophila embryos and analyzed its subunit composition. The BRM complex contains at least seven major polypeptides. Surprisingly, the majority of the subunits of the BRM complex are not encoded by trithorax group genes. Furthermore, a screen for enhancers of a dominant-negative brm mutation identified only one trithorax group gene, moira (mor), that appears to be essential for brm function in vivo. Four of the subunits of the BRM complex are related to subunits of the yeast chromatin remodeling complexes SWI/SNF and RSC. The BRM complex is even more highly related to the human BRG1 and hBRM complexes, but lacks the subunit heterogeneity characteristic of these complexes. We present biochemical evidence for the existence of two additional complexes containing trithorax group proteins: a 2 MDa ASH1 complex and a 500 kDa ASH2 complex. These findings suggest that BRM plays a role in chromatin remodeling that is distinct from the function of most other trithorax group proteins.

scholarly journals BAF60a Mediates Critical Interactions between Nuclear Receptors and the BRG1 Chromatin-Remodeling Complex for Transactivation

2003 ◽  
Vol 23 (17) ◽  
pp. 6210-6220 ◽  
Author(s):  
Pei-Wen Hsiao ◽  
Christy J. Fryer ◽  
Kevin W. Trotter ◽  
Weidong Wang ◽  
Trevor K. Archer
Keyword(s):  
Nuclear Receptors ◽  
Chromatin Remodeling ◽  
Molecular Mechanisms ◽  
Hormone Receptors ◽  
Nuclear Receptor Coactivators ◽  
Chromatin Remodeling Complex ◽  
Truncation Mutant ◽  
Promoter Recruitment

ABSTRACT Nuclear hormone receptors are ligand-dependent transcriptional regulators that modulate chromatin structure. However, the precise molecular mechanisms by which receptors recruit chromatin-remodeling activity are not fully elucidated. We show that in the absence of its ligand-binding domain, the glucocorticoid receptor (GR) is able to interact with both nuclear receptor coactivators and the BRG1 chromatin-remodeling complex in vivo. Individually, the GR makes direct interactions with BRG1-associated factor 60a (BAF60a) and BAF57, but not with BRG1, BAF155, or BAF170. Further, BAF60a possesses at least two interaction surfaces, one for GR and BRG1 and a second for BAF155 and BAF170. A GR mutant, GR(R488Q), that fails to interact with BAF60a in vitro has reduced chromatin-remodeling activity and reduced transcriptional activity from the promoter assembled as chromatin in vivo. Stable expression of a BAF60a truncation mutant, BAF60a4-140, caused chromatin-specific loss of GR functions in vivo. In the presence of the BAF60a mutant, the GR fails to interact with the BRG1 complex and consequently is also deficient in its ability to activate transcription from chromatin. Thus, in addition to previously identified BAF250, BAF60a may provide another critical and direct link between nuclear receptors and the BRG1 complex that is required for promoter recruitment and subsequent chromatin remodeling.

scholarly journals Determinants of CoRNR-Dependent Repression Complex Assembly on Nuclear Hormone Receptors

2001 ◽  
Vol 21 (5) ◽  
pp. 1747-1758 ◽  
Author(s):  
Xiao Hu ◽  
Yun Li ◽  
Mitchell A. Lazar
Keyword(s):  
Retinoic Acid ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Retinoic Acid Receptor ◽  
Nuclear Hormone Receptor ◽  
Nuclear Hormone Receptors ◽  
Complex Assembly ◽  
Acid Receptor ◽  
Repression Complex ◽  
The Individual

ABSTRACT Ligand-dependent exchange of coactivators and corepressors is the fundamental regulator of nuclear hormone receptor (NHR) function. The interaction surfaces of coactivators and corepressors are similar but distinct enough to allow the ligand to function as a switch. Multiple NHRs share features that allow corepressor binding, and each of two distinct corepressors (N-CoR and SMRT) contains two similar CoRNR motifs that interact with NHRs. Here we report that the specificity of corepressor-NHR interaction is determined by the individual NHR interacting with specific CoRNR boxes within a preferred corepressor. First, receptors have distinct preferences for CoRNR1 versus CoRNR2. For example, the retinoic acid receptor binds CoRNR1, while RXR interacts almost exclusively with CoRNR2. Second, the NHR preference for N-CoR or SMRT is due to differences in CoRNR1 but not CoRNR2. Moreover, within a single corepressor, affinity for different NHRs is determined by distinct regions flanking CoRNR1. The highly specific determinants of NHR-corepressor interaction and preference suggest that repression is regulated by the permissibility of selected receptor-CoRNR-corepressor combinations. Interestingly, different NHR surfaces contribute to binding of CoRNR1 and CoRNR2, suggesting a model to explain corepressor binding to NHR heterodimers.

scholarly journals Fos is a preferential target of glucocorticoid receptor inhibition of AP-1 activity in vitro.

1993 ◽  
Vol 13 (6) ◽  
pp. 3782-3791 ◽  
Author(s):  
T K Kerppola ◽  
D Luk ◽  
T Curran
Keyword(s):  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Leucine Zipper ◽  
Molecular Mechanisms ◽  
Hormone Receptors ◽  
Transcription Activation ◽  
Nuclear Hormone Receptor ◽  
Binding Domain ◽  
Dna Binding Domain

Several regulatory interactions between the AP-1 and the nuclear hormone receptor families of transcription factors have been reported. However, the molecular mechanisms that underlie these interactions remain unknown, and models derived from transient-transfection experiments are contradictory. We have investigated the effect of the purified glucocorticoid receptor (GR) DNA-binding domain (GR residues 440 to 533 [GR440-533]) on DNA binding and transcription activation by Fos-Jun heterodimers and Jun homodimers. GR440-533 differentially inhibited DNA binding and transcription activation by Fos-Jun heterodimers. Inhibition of Jun homodimers required a 10-fold-higher concentration of GR440-533. An excess of Fos monomers protected Fos-Jun heterodimers from inhibition by GR440-533. Surprisingly, regions outside the leucine zipper and basic region were required for GR inhibition of Fos and Jun DNA binding. The region of GR440-533 required for inhibition of Fos-Jun DNA binding was localized to the zinc finger DNA-binding domain. However, inhibition of Fos-Jun DNA binding was independent of DNA binding by GR440-533. GR440-533 also differentially inhibited Fos-Jun heterodimer binding to the proliferin plfG element. Differential inhibition of DNA binding by different AP-1 family complexes provides a potential mechanism for the diverse interactions between nuclear hormone receptors and AP-1 family proteins at different promoters and in different cell types.

Sign in / Sign up

Export Citation Format

Share Document