Differential HDAC1 and 2 Recruitment by Members of the MIER Family.

The mier family consists of three related genes encoding ELM2-SANT containing proteins. MIER1 has been well characterized and is known to function in transcriptional repression through its ability to recruit HDAC1 and 2. Little is known about MIER2 or MIER3 function and no study characterizing these two proteins has been published.

Insulin and IGF-1, but not 17β-estradiol, alter the subcellular localization of MIER1α in MCF7 breast carcinoma cells.

Background: MIER1α is a transcriptional regulator that interacts with estrogen receptor α and inhibits estrogen-stimulated growth of breast carcinoma cells. Interestingly, analysis of MIER1α subcellular localization in breast samples revealed a stepwise shift from the nucleus to the cytoplasm during progression to invasive carcinoma. Previously, we demonstrated that MIER1α is nuclear in MCF7 cells yet it does not contain a nuclear localization signal.

Nuclear localization of the transcriptional regulator MIER1α requires interaction with HDAC1/2 in breast cancer cells.

MIER1α is a transcriptional regulator that functions in gene repression through its ability to interact with various chromatin modifiers and transcription factors. We have also shown that MIER1α interacts with ERα and inhibits estrogen-stimulated growth. While MIER1α is localized in the nucleus of MCF7 cells, previous studies have shown that it does not contain a nuclear localization signal.

Protein expression pattern of human MIER1 alpha, a novel estrogen receptor binding protein.

MIER1 is a transcriptional regulator that exists as several isoforms. Of particular interest is the MIER1α isoform, which contains in its unique C-terminus an LXXLL motif for interaction with nuclear hormone receptors. Indeed, MIER1α has been shown to interact with ERα and inhibit estrogen-stimulated growth of breast carcinoma cells.

Differential splicing alters subcellular localization of the alpha but not beta isoform of the MIER1 transcriptional regulator in breast cancer cells.

MIER1 was originally identified in a screen for novel fibroblast growth factor activated early response genes. The mier1 gene gives rise to multiple transcripts encoding protein isoforms that differ in their amino (N-) and carboxy (C-) termini. Much of the work to date has focused on the two C-terminal variants, MIER1α and β, both of which have been shown to function as transcriptional repressors.

The transcriptional cofactor MIER1-beta negatively regulates histone acetyltransferase activity of the CREB-binding protein.

Background: Mier1 encodes a novel transcriptional regulator and was originally isolated as a fibroblast growth factor early response gene. Two major protein isoforms have been identified, MIER1alpha and beta, which differ in their C-terminal sequence. Previously, we demonstrated that both isoforms recruit histone deacetylase 1 (HDAC1) to repress transcription.

Regulation of the response to Nodal-mediated mesoderm induction by Xrel3.

The Xenopus egg has a yolk-laden vegetal hemisphere juxtaposed to a darkly pigmented animal hemisphere. Mesoderm is derived from the marginal zone, located at the interface between the two hemispheres. The vegetal-most cells become endoderm and release TGF-beta-related factors, including the Xenopus Nodal related (Xnr) proteins, which diffuse to induce the marginal zone to form mesoderm.

Protein expression of the transcriptional regulator MI-ER1 alpha in adult mouse tissues.

MI-ER1 is a novel transcriptional regulator that plays a critical role in embryonic development and is differentially expressed in breast carcinoma. The MI-ER1 protein sequence is highly conserved among species, with 95% identity between mouse and humans and 72% between Xenopus and mouse. There are two major protein isoforms, MI-ER1alpha and MI-ER1beta, which differ in the sequence of their C-terminus.

Cloning and characterization of the mouse ortholog of mi-er1.

Mi-er1 is a fibroblast growth factor immediate-early gene whose expression is differentially regulated in breast tumours. MI-ER1 functions as a transcriptional repressor of a number of genes, including Sp1 target genes. The Xenopus and human orthologs have been described and here we report the characterization of the mouse gene and its products.

Developmentally regulated cytoplasmic retention of the transcription factor XMI-ER1 requires sequence in the acidic activation domain.

Xmi-er1 is a fibroblast growth factor regulated immediate-early gene that is activated during mesoderm induction in Xenopus embryonic explants. This gene encodes a nuclear protein with potent transcriptional regulator activity and overexpression of XMI-ER1 in Xenopus embryos inhibits mesoderm induction and leads to truncations along the anteroposterior axis. We showed previously that XMI-ER1 is retained in the cytoplasm during cleavage stages and only begins to appear in the nucleus at mid-blastula.

The SANT domain of human MI-ER1 interacts with Sp1 to interfere with GC box recognition and repress transcription from its own promoter.

To gain insight into the regulation of hmi-er1 expression, we cloned a human genomic DNA fragment containing one of the two hmi-er1 promoters and consisting of 1460 bp upstream of the translation initiation codon of hMI-ER1. Computer-assisted sequence analysis revealed that the hmi-er1 promoter region contains a CpG island but lacks an identifiable TATA element, initiator sequence and downstream promoter element. This genomic DNA was able to direct transcription of a luciferase reporter gene in a variety of human cell lines, and the minimal promoter was shown to be located within-68/+144 bp.

Proline365 is a critical residue for the activity of XMI-ER1 in Xenopus embryonic development.

Xmi-er1 is an immediate-early gene encoding a transcriptional regulator whose expression is activated by fibroblast growth factor (FGF) during mesoderm induction in Xenopus. In this study, we examined the role of xmi-er1 in embryonic development and mesoderm induction and investigated the importance of various functional domains in the protein sequence. Overexpression of xmi-er1 in embryos resulted in truncations of the anteroposterior axis, with most of the abnormal embryos exhibiting deficiencies in both anterior and posterior structures.

Human MI-ER1 alpha and beta function as transcriptional repressors by recruitment of histone deacetylase 1 to their conserved ELM2 domain.

mi-er1 (previously called er1) was first isolated from Xenopus laevis embryonic cells as a novel fibroblast growth factor-regulated immediate-early gene. Xmi-er1 was shown to encode a nuclear protein with an N-terminal acidic transcription activation domain. The human orthologue of mi-er1 (hmi-er1) displays 91% similarity to the Xenopus sequence at the amino acid level and was shown to be upregulated in breast carcinoma cell lines and tumors.

Genomic organization of the human mi-er1 gene and characterization of alternatively spliced isoforms: regulated use of a facultative intron determines subcellular localization.

mi-er1 (previously called er1) is a fibroblast growth factor-inducible early response gene activated during mesoderm induction in Xenopus embryos and encoding a nuclear protein that functions as a transcriptional activator. The human orthologue of mi-er1 was shown to be upregulated in breast carcinoma cell lines and breast tumours when compared to normal breast cells. In this report, we investigate the structure of the human mi-er1 (hmi-er1) gene and characterize the alternatively spliced transcripts and protein isoforms.