scholarly journals CREB binding protein acts synergistically with steroid receptor coactivator-1 to enhance steroid receptor-dependent transcription.

1996 ◽  
Vol 93 (17) ◽  
pp. 8884-8888 ◽  
Author(s):  
C. L. Smith ◽  
S. A. Onate ◽  
M. J. Tsai ◽  
B. W. O'Malley
Keyword(s):  
Binding Protein ◽  
Steroid Receptor ◽  
Creb Binding Protein ◽  
Steroid Receptor Coactivator

scholarly journals Analysis of the Steroid Receptor Coactivator 1 (SRC1)-CREB Binding Protein Interaction Interface and Its Importance for the Function of SRC1

2001 ◽  
Vol 21 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Hilary M. Sheppard ◽  
Janet C. Harries ◽  
Sagair Hussain ◽  
Charlotte Bevan ◽  
David M. Heery
Keyword(s):  
Binding Protein ◽  
Steroid Receptor ◽  
Creb Binding Protein ◽  
Interaction Domain ◽  
Steroid Receptor Coactivator ◽  
Helix Loop Helix ◽  
Rich Domain ◽  
Interaction Interface ◽  
Acetyltransferase Domain

ABSTRACT The transcriptional activity of nuclear receptors is mediated by coactivator proteins, including steroid receptor coactivator 1 (SRC1) and its homologues and the general coactivators CREB binding protein (CBP) and p300. SRC1 contains an activation domain (AD1) which functions via recruitment of CBP and and p300. In this study, we have used yeast two-hybrid and in vitro interaction-peptide inhibition experiments to map the AD1 domain of SRC1 to a 35-residue sequence potentially containing two α-helices. We also define a 72-amino-acid sequence in CBP necessary for SRC1 binding, designated the SRC1 interaction domain (SID). We show that in contrast to SRC1, direct binding of CBP to the estrogen receptor is weak, suggesting that SRC1 functions primarily as an adaptor to recruit CBP and p300. In support of this, we show that the ability of SRC1 to enhance ligand-dependent nuclear receptor activity in transiently transfected cells is dependent upon the integrity of the AD1 region. In contrast, the putative histone acetyltransferase domain, the Per-Arnt-Sim basic helix-loop-helix domain, the glutamine-rich domain, and AD2 can each be removed without loss of ligand-induced activity. Remarkably, a construct corresponding to residues 631 to 970, which contains only the LXXLL motifs and the AD1 region of SRC1, retained strong coactivator activity in our assays.

scholarly journals Nuclear Integration of Glucocorticoid Receptor and Nuclear Factor-κB Signaling by CREB-binding Protein and Steroid Receptor Coactivator-1

1998 ◽  
Vol 273 (45) ◽  
pp. 29291-29294 ◽  
Author(s):  
Kelly-Ann Sheppard ◽  
Kathleen M. Phelps ◽  
Amy J. Williams ◽  
Dimitris Thanos ◽  
Christopher K. Glass ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Binding Protein ◽  
Steroid Receptor ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Creb Binding Protein ◽  
Steroid Receptor Coactivator

scholarly journals Estradiol Regulates Corticotropin-Releasing Hormone Gene (crh) Expression in a Rapid and Phasic Manner that Parallels Estrogen Receptor-α and -β Recruitment to a 3′,5′-Cyclic Adenosine 5′-Monophosphate Regulatory Region of the Proximal crh Promoter

Endocrinology ◽  
2007 ◽  
Vol 149 (1) ◽  
pp. 346-357 ◽  
Author(s):  
Avin S. Lalmansingh ◽  
Rosalie M. Uht
Keyword(s):  
Molecular Mechanisms ◽  
Binding Protein ◽  
Regulatory Element ◽  
Regulatory Region ◽  
Steroid Receptor ◽  
Early Gene ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Steroid Receptor Coactivator ◽  
Histone 3

In the central nervous system, CRH regulates several affective states. Dysregulation of neuronal crh expression in the paraventricular nucleus of the hypothalamus correlates with some forms of depression, and amygdalar crh expression may modulate levels of anxiety. Because estrogens modulate these states, we sought to determine 17β-estradiol (E2) effects on crh expression. CRH mRNA levels were measured in the AR-5 amygdaloid cell line by RT-PCR analysis. They increased by 1 min of E2 treatment, suggesting that crh behaves as an immediate-early gene. After peaking at 3 min, CRH mRNA returned to basal levels and then increased by 60 min. To dissect some of the molecular mechanisms underlying these events, we measured occupancy of the crh promoter by estrogen receptors (ERs) and coactivators, using chromatin immunoprecipitation. Because this promoter does not contain palindromic estrogen response elements, we targeted the region of a cAMP regulatory element (CRE), implicated in crh regulation. The temporal pattern of the mRNA response was mimicked by recruitment of ERα and -β, phospho-CRE-binding protein, coactivators steroid receptor coactivator-1 and CRE-binding protein-binding protein (CBP), and an increase in histone 3 and 4 acetylation. Lastly, ERα and -β loading were temporally dissociated, peaking at 1 and 3 min, respectively. The ER peaks were associated with coactivators and acetylation patterns. ERα associated with phospho-CRE-binding protein, CBP, steroid receptor coactivator-1, and increased acetylated histone 3. ERβ associated with CBP and increased acetylated histone 4. The tight temporal correlation between E2-induced CRH mRNA levels and promoter occupancy by ERs strongly suggest that E2 regulates crh expression through an ERα- and/or ERβ-CRE alternate pathway.

scholarly journals Sex-Dependent Mechanisms of Glucocorticoid Regulation of the Mouse Hypothalamic Corticotropin-Releasing Hormone Gene

Endocrinology ◽  
2019 ◽  
Vol 161 (1) ◽  
Author(s):  
Ashley L Heck ◽  
Maranda K Thompson ◽  
Rosalie M Uht ◽  
Robert J Handa
Keyword(s):  
Binding Protein ◽  
Day Treatment ◽  
Immunohistochemical Analysis ◽  
Creb Binding Protein ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Steroid Receptor Coactivator ◽  
Transcriptional Coregulators ◽  
Nuclear Ribonucleoprotein ◽  
Transcription 3

Abstract To limit excessive glucocorticoid secretion following hypothalamic-pituitary-adrenal (HPA) axis stimulation, circulating glucocorticoids inhibit corticotropin-releasing hormone (CRH) expression in paraventricular nucleus (PVN) neurons. As HPA function differs between sexes and depends on circulating estradiol (E2) levels in females, we investigated sex/estrous stage-dependent glucocorticoid regulation of PVN Crh. Using NanoString nCounter technology, we first demonstrated that adrenalectomized (ADX’d) diestrous female (low E2), but not male or proestrous female (high E2), mice exhibited a robust decrease in PVN CRH mRNA following 2-day treatment with the glucocorticoid receptor (GR) agonist RU28362. Immunohistochemical analysis of PVN CRH neurons in Crh-IRES-Cre;Ai14 mice, where TdTomato fluorescence permanently tags CRH-expressing neurons, showed similarly abundant co-expression of GR-immunoreactivity in males, diestrous females, and proestrous females. However, we identified sex/estrous stage-related glucocorticoid regulation or expression of GR transcriptional coregulators. Out of 17 coregulator genes examined using nCounter multiplex analysis, mRNAs that were decreased by RU28362 in ADX’d mice in a sex/estrous stage-dependent fashion included: GR (males = diestrous females > proestrous females), signal transducer and activator of transcription 3 (STAT3) (males < diestrous = proestrous), and HDAC1 (males < diestrous > proestrous). Steroid receptor coactivator 3 (SRC-3), nuclear corepressor 1 (NCoR1), heterogeneous nuclear ribonucleoprotein U (hnrnpu), CREB binding protein (CBP) and CREB-regulated transcription coactivator 2 (CRTC2) mRNAs were lower in ADX’d diestrous and proestrous females versus males. Additionally, most PVN CRH neurons co-expressed methylated CpG binding protein 2 (MeCP2)-immunoreactivity in diestrous female and male Crh-IRES-Cre;Ai14 mice. Our findings collectively suggest that GR’s sex-dependent regulation of PVN Crh may depend upon differences in the GR transcriptional machinery and an underlying influence of E2 levels in females.

scholarly journals Transcriptional activation by estrogen receptor (ERalpha) and steroid receptor coactivator (SRC1) involves distinct mechanisms in yeast and mammalian cells

2003 ◽  
Vol 30 (3) ◽  
pp. 411-422 ◽  
Author(s):  
HM Sheppard ◽  
S Matsuda ◽  
JC Harries ◽  
KB Kindle ◽  
DM Heery
Keyword(s):  
Transcriptional Activation ◽  
Mammalian Cells ◽  
Transcriptional Activity ◽  
Steroid Receptors ◽  
Steroid Receptor ◽  
Yeast Cells ◽  
Creb Binding Protein ◽  
Subtle Difference ◽  
Steroid Receptor Coactivator ◽  
Helix 12

Steroid receptors activate transcription in yeast cells via interactions with endogenous coactivators and/or basal factors. We examined the effects of mutations in the ligand binding domain on the transcriptional activity of ERalpha in yeast. Our results show that mutations in Helix 3 (K366A) and Helix 12 (M547A, L548A) disrupt transcriptional activity of ERalpha in yeast, as previously observed in mammalian cells. However, replacement of a conserved tyrosine residue in Helix 12 with alanine or aspartate (Y541A and Y541D), which renders ERalpha constitutively active in mammalian cells, had only a weak stimulatory effect on ligand-independent reporter activation by ERalpha in yeast. Two-hybrid interaction experiments revealed that a Y541A mutant expressed in yeast was capable of ligand-independent binding to a mammalian coactivator, suggesting that there is a subtle difference in how this mutant interacts with mammalian and yeast cofactors. We also show that the ligand-dependent activities of ERalpha and progesterone receptor (PR) in yeast cells were strongly enhanced by the human p160 protein steroid receptor coactivator (SRC1), but not by CREB-Binding Protein (CBP) or the p300/CBP associated factor (P/CAF). Although the SRC1 activation domains AD1 and AD2 are functional in yeast, deletion of these sequences only partially impaired SRC1 coactivator function in this organism; this is in contrast to similar experiments in mammalian cells. Thus SRC1 sequences involved in recruitment of CBP/p300 and Co-Activator-Associated Arginine Methyltransferase (CARM-1) in mammalian cells are not essential for its function in yeast, suggesting that SRC1 operates via distinct mechanisms in yeast and mammalian cells.

Molecular Basis for Cold-Intolerant Yang-Deficient Constitution of Traditional Chinese Medicine

2008 ◽  
Vol 36 (05) ◽  
pp. 827-834 ◽  
Author(s):  
Qi Wang ◽  
Shilin Yao
Keyword(s):  
Gene Expression ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Thyroid Hormone Receptor ◽  
Binding Protein ◽  
Expression Profiles ◽  
White Blood Cells ◽  
Steroid Receptor ◽  
Biochemical Basis ◽  
Steroid Receptor Coactivator

Based on the theory of constitution of Traditional Chinese Medicine (TCM), the human population can be classified into nine constitutions including a balanced constitution and eight unbalanced constitutions (Yang-deficient, Yin-deficient, Qi-deficient, Phlegm-wetness, Wetness-heat, Stagnant blood, Depressed, and Inherited special constitutions). Generally, unbalanced constitutions are more susceptible to certain diseases than balanced constitutions. However, whether such constitution classification has modern genetic and biochemical basis is poorly understood. Here we examined gene expression profiles in peripheral white blood cells from eight individuals with Yang-deficient constitutions and six individuals with balanced constitutions using Affymetrix U133 plus 2.0 expression array. Based on a q < 0.05 and fold-change ≥ 2 cutoff, we have identified that 785 genes are up-regulated and 954 genes are down-regulated in Yang-deficient constitution compared to a balanced constitution. Importantly, we found that the expression of thyroid hormone receptor beta (TRβ) and several key nuclear receptor coactivators including steroid receptor coactivator 1 (SRC1), steroid receptor coactivator 3 (SRC3), cAMP-response element-binding protein (CREB) binding protein (CBP) and Mediator is significantly decreased. Such decreased expression of TR transcription complex may lead to impaired thermogenesis, providing a molecular explanation of the main symptom associated with Yang-deficient constitution, cold intolerance. Future studies are needed to validate these gene expression changes in additional populations and address the underlying mechanisms for differential gene expression.

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