Synergistic enhansons located within an acute phase responsive enhancer modulate glucocorticoid induction of angiotensinogen gene transcription - PubMed (original) (raw)
Synergistic enhansons located within an acute phase responsive enhancer modulate glucocorticoid induction of angiotensinogen gene transcription
A R Brasier et al. Mol Endocrinol. 1990 Dec.
Abstract
The hepatic transcription of the angiotensinogen gene is regulated by both glucocorticoids and cytokines generated as products of the acute phase reaction. We have identified a multimodular enhancer in the 5'-flanking region of the rat angiotensinogen gene that mediates these responses and consists of an acute phase response element (APRE) flanked on both sides by adjacent glucocorticoid response element consensus motifs (GREs). Induction of transcription by the cytokine interleukin-1 (IL-1) is glucocorticoid dependent and mediated through the APRE. The APRE binds in a mutually exclusive manner a cytokine/phorbol ester-inducible protein (BPi), indistinguishable from nuclear factor kB, and a family of constitutive liver proteins (BPcs) related to the heat-stable transcription factor C/EBP. Using mutated 5'-flanking sequences of the angiotensinogen gene fused to a firefly luciferase reporter gene transfected into hepatoblastoma (HepG2) cells, we have mapped enhanson sequences required for the transcriptional response to glucocorticoids. Two functionally distinct GREs are identified by deletion and site-directed mutagenesis, both of which mediate glucocorticoid-stimulated transcription in vivo. Glucocorticoid-induced transcription mediated by the angiotensinogen gene enhancer is, furthermore, dependent on the occupancy of the APRE by either the BPi or a member of the BPc family because a mutant APRE that binds neither BPi nor BPc exhibits an attenuated glucocorticoid responsiveness. Mutant APREs that permit exclusive binding of either BPi or BPc synergistically transmit the glucocorticoid response mediated by one or the other of the adjacent GREs. Thus, the induction of angiotensinogen gene transcription involves interaction between the glucocorticoid receptor and either one of the APRE-binding proteins: either the cytokine-inducible NFkB or the constitutive family of C/EBP-like proteins, bound to adjacent enhansons in a mutually synergistic enhancer complex.
Similar articles
- The permissive role of glucocorticoids on interleukin-1 stimulation of angiotensinogen gene transcription is mediated by an interaction between inducible enhancers.
Ron D, Brasier AR, Wright KA, Habener JF. Ron D, et al. Mol Cell Biol. 1990 Aug;10(8):4389-95. doi: 10.1128/mcb.10.8.4389-4395.1990. Mol Cell Biol. 1990. PMID: 2370871 Free PMC article. - Transcriptional regulation of hepatic angiotensinogen gene expression by the acute-phase response.
Ron D, Brasier AR, Habener JF. Ron D, et al. Mol Cell Endocrinol. 1990 Dec 21;74(3):C97-104. doi: 10.1016/0303-7207(90)90221-s. Mol Cell Endocrinol. 1990. PMID: 2128877 Review. - Mechanisms for inducible control of angiotensinogen gene transcription.
Brasier AR, Li J. Brasier AR, et al. Hypertension. 1996 Mar;27(3 Pt 2):465-75. doi: 10.1161/01.hyp.27.3.465. Hypertension. 1996. PMID: 8613188 Review.
Cited by
- Potential mechanisms of hypothalamic renin-angiotensin system activation by leptin and DOCA-salt for the control of resting metabolism.
Sapouckey SA, Deng G, Sigmund CD, Grobe JL. Sapouckey SA, et al. Physiol Genomics. 2017 Dec 1;49(12):722-732. doi: 10.1152/physiolgenomics.00087.2017. Epub 2017 Oct 6. Physiol Genomics. 2017. PMID: 28986397 Free PMC article. Review. - Dynamic regulation of the angiotensinogen gene by DNA methylation, which is influenced by various stimuli experienced in daily life.
Demura M, Demura Y, Takeda Y, Saijoh K. Demura M, et al. Hypertens Res. 2015 Aug;38(8):519-27. doi: 10.1038/hr.2015.42. Epub 2015 Mar 26. Hypertens Res. 2015. PMID: 25809578 Review. - Stratified control of IGF-I expression by hypoxia and stress hormones in osteoblasts.
McCarthy TL, Yun Z, Madri JA, Centrella M. McCarthy TL, et al. Gene. 2014 Apr 10;539(1):141-51. doi: 10.1016/j.gene.2014.01.011. Epub 2014 Jan 15. Gene. 2014. PMID: 24440782 Free PMC article. - Transgenic mice with -6A haplotype of the human angiotensinogen gene have increased blood pressure compared with -6G haplotype.
Jain S, Tillinger A, Mopidevi B, Pandey VG, Chauhan CK, Fiering SN, Warming S, Kumar A. Jain S, et al. J Biol Chem. 2010 Dec 24;285(52):41172-86. doi: 10.1074/jbc.M110.167585. Epub 2010 Oct 26. J Biol Chem. 2010. PMID: 20978123 Free PMC article. - MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NF-kappa B activation.
Yujiri T, Ware M, Widmann C, Oyer R, Russell D, Chan E, Zaitsu Y, Clarke P, Tyler K, Oka Y, Fanger GR, Henson P, Johnson GL. Yujiri T, et al. Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7272-7. doi: 10.1073/pnas.130176697. Proc Natl Acad Sci U S A. 2000. PMID: 10852963 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical