Gillespie LL , Paterno GD .

97938-1 Canadian Institutes of Health Research , 97938-1 PHS HHS

	A. Schematic illustrating the exon-intron organization of the human MIER1 geneExons are shown as red bars/vertical lines and introns as horizontal lines; exon numbers are indicated below each schematic. The light red bar indicates the facultative intron 16 and the position of the alpha and beta carboxy-terminal coding regions are indicated. Note that the beta coding region is located within the facultative intron. The three alternate starts of translation, ML-, MF- and MAE- are indicated as are the three polyadenylation signals (PAS): i, ii and iii.
	B. Schematic illustrating the variant 5′ and 3′ ends of human MIER1 transcriptsAlternate 5′ ends are generated from differential promoter usage (P1 or P2) or alternate inclusion of exon 3A. This leads to three alternate starts of translation, indicated as ML-, MF- and MAE-, and produces three distinct amino termini. The four variant 3′ ends, a, bi, bii and biii, produced by alternative splicing or alternate PAS usage, result in transcripts readily distinguished by size (1.7 kb, 2.5 kb, 3.4 kb and 4.8 kb, respectively) on a Northern blot. It should be noted that three of the variant 3′ ends, bi, bii and biii encode the same protein sequence and differ only in their untranslated region. * indicates beta encoding transcript that contains the alpha exon in its 3′UTR. The locations of the alpha and beta carboxy-terminal coding regions and PAS i, ii and iii are indicated. The combination of three possible 5′ ends with four possible 3′ ends gives rise to 12 distinct transcripts, but only 6 distinct protein isoforms. In most adult tissues, the most abundant transcript is 4.8 kb. Additional transcripts have been reported in Ensembl.
	Schematic illustrating the common internal domains of the MIER1 isoforms and the variant amino- (N-) and carboxy- (C-) terminiTranscription from the P1 promoter produces proteins that either begin with M-L- or with the sequence encoded by exon 3A (MFMFNWFTDCLWTLFLSNYQ). Transcription from the P2 promoter produces a protein that begins with M-A-E-. The variant N-termini of the MIER1 isoforms are followed by common internal sequence containing several distinct domains: acidic, which function in transcriptional activation (Paterno et al., 1997); ELM2, responsible for recruitment of HDAC1 (Ding et al., 2003); SANT, which interacts with Sp1 (Ding et al., 2004) and PSPPP, which is required for MIER1 activity in the Xenopus embryo (Teplitsky et al., 2003). The two alternate C-termini, alpha and beta, result from removal or inclusion and read-through of intron 16, respectively. The alpha C-terminus contains a classic LXXLL motif for interaction with nuclear receptors; the beta C-terminus contains a nuclear localization signal (NLS).

Beausoleil, Large-scale characterization of HeLa cell nuclear phosphoproteins. 2004, Pubmed

Beausoleil, Large-scale characterization of HeLa cell nuclear phosphoproteins. 2004, Pubmed
Blackmore, The transcriptional cofactor MIER1-beta negatively regulates histone acetyltransferase activity of the CREB-binding protein. 2008, Pubmed
Ding, The SANT domain of human MI-ER1 interacts with Sp1 to interfere with GC box recognition and repress transcription from its own promoter. 2004, Pubmed
Ding, Human MI-ER1 alpha and beta function as transcriptional repressors by recruitment of histone deacetylase 1 to their conserved ELM2 domain. 2003, Pubmed , Xenbase
Luchman, Differential nuclear localization of ER1 protein during embryonic development in Xenopus laevis. 1999, Pubmed , Xenbase
McCarthy, Changes in subcellular localisation of MI-ER1 alpha, a novel oestrogen receptor-alpha interacting protein, is associated with breast cancer progression. 2008, Pubmed
Nousiainen, Phosphoproteome analysis of the human mitotic spindle. 2006, Pubmed
Paterno, Molecular cloning of human er1 cDNA and its differential expression in breast tumours and tumour-derived cell lines. 1998, Pubmed , Xenbase
Paterno, Genomic organization of the human mi-er1 gene and characterization of alternatively spliced isoforms: regulated use of a facultative intron determines subcellular localization. 2002, Pubmed , Xenbase
Paterno, cDNA cloning of a novel, developmentally regulated immediate early gene activated by fibroblast growth factor and encoding a nuclear protein. 1997, Pubmed , Xenbase
Post, Nuclear localization signals in the Xenopus FGF embryonic early response 1 protein. 2001, Pubmed , Xenbase
Post, Developmentally regulated cytoplasmic retention of the transcription factor XMI-ER1 requires sequence in the acidic activation domain. 2005, Pubmed , Xenbase
Teplitsky, Proline365 is a critical residue for the activity of XMI-ER1 in Xenopus embryonic development. 2003, Pubmed , Xenbase
Thorne, Protein expression of the transcriptional regulator MI-ER1 alpha in adult mouse tissues. 2008, Pubmed , Xenbase
Thorne, Cloning and characterization of the mouse ortholog of mi-er1. 2005, Pubmed , Xenbase
Wang, Atrophin recruits HDAC1/2 and G9a to modify histone H3K9 and to determine cell fates. 2008, Pubmed