Involvement of a C/EBP-like protein in the acquisition of responsiveness to glucocorticoid hormones during chick neural retina development.

Abstract

The glucocorticoid receptor in chicken embryonic neural retina is expressed early in ontogeny, yet the tissue's response to the glucocorticoid hormone, i.e., induction of glutamine synthetase (GS), develops later, only during week 2 of ontogeny. Transient transfection of embryonic day 7 (E7) retinal cells, which are nonresponsive to glucocorticoids, with chimeric plasmids containing the chloramphenicol acetyltransferase reporter gene under the control of glucocorticoid-responsive promoters demonstrated that GR in E7 cells is a functional transactivating factor. We show that the limiting transcription factor that controls the developmental acquisition of responsiveness to glucocorticoids is similar to a CCAAT enhancer-binding protein (C/EBP). This protein recognizes a sequence in the promoter of the chick GS gene, which is required for eliciting the glucocorticoid response. Retinal C/EBP-like protein was not detected in the glucocorticoid-nonresponsive (E7) proliferating glioblasts but was found to be present in the glucocorticoid-responsive (E12) postmitotic cells.

Developmental changes in the expression and compartmentalization of the glucocorticoid receptor in embryonic retina.

“…However, the sum total of the two isoforms was similar in E6 and E10 retina (Fig. 2B), consistent with previous findings that GR protein level (26) and hormone binding activity (23)(24)(25) were similar at these two ages.…”

“…Supporting this possibility is the finding that overexpression of GR in E6 retina (normally noninducible) resulted in induction of a CAT construct controlled by the promoter of the chicken glutamine synthetase gene (19,22). This developmental increase in GR transcriptional activity is, however, in apparent contrast with findings that the level of hormone binding activity and, presumably, that of GR are similar in E6 and E10 retina (23)(24)(25)(26) (32). The unbound hormone was removed (see Materials and Methods), and the samples were electrophoresed and analyzed.…”

Structure/Activity Elements of the Multifunctional Protein, GMEB-1

“…These responses most commonly involve either the induction or repression of gene expression due to changes in transcription. The particular response of a given cell depends upon on a variety of tissue and developmental controls that dictate which genes are capable of regulation by receptor-steroid complexes (1)(2)(3). Among those genes that are programmed to respond, many of the details of steroid hormone action have only recently emerged and include binding to specific DNA sequences called hormone response elements (HREs), 1 reorganization of chromatin, recruitment of a burgeoning assortment of transcription cofactors, and interaction with components of the transcription complex (4 -7).…”

Characterization of an NF-1/CTF Family Member as a Functional Activator of the Mouse Mammary Tumor Virus Long Terminal Repeat 5′ Enhancer

“…Indeed, transcriptional induction through the steroid hormone-responsive elements of the MMTV LTR is dependent on the presence of the NF-1 binding site in the proximal MMTV LTR promoter (43)(44)(45)(46). Reports from other promoter systems have also indicated an interaction or cooperation between the glucocorticoid receptor and the C/EBP subset of the CCAAT binding proteins for proper glucocorticoid receptor function (28,47).…”