Molecular phylogeny of the ETS gene family

Laudet, Vincent; Hänni, Catherine; Stéhelin, D; Duterque-Coquillaud, Martine

doi:10.1038/sj.onc.1202444

Cited by 128 publications

(116 citation statements)

References 65 publications

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“…The region of ERM interacting with ZNF237 in yeast two-hybrid has been narrowed to a region including the CIDD and the Ets domain (data not shown). This is consistent with TEL and ERM sharing the most significant homology in their Ets domain [18]. Understanding the function of the ZNF237 proteins in the modulation of the activity of Ets factors will require identification of the amino acid region of ERM involved in the interaction with ZNF237 and examination of the interactions with other Ets members including members of the small PEA3 group most related to ERM such as ER81 which we have already shown to activate PS1 transcription [26].…”

Section: Discussionsupporting

confidence: 78%

Analysis of transcriptional modulation of the presenilin 1 gene promoter by ZNF237, a candidate binding partner of the Ets transcription factor ERM

Pastorcic

Das

2007

Brain Research

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DNA sequences required for the expression of the human presenilin 1 (PS1) gene have been identified between -118 and +178 flanking the major initiation site (+1) mapped in SK-N-SH cells. Several Ets sites are located both upstream as well as downstream from the +1 site, including an Ets motif present at -10 that controls 90% of transcription in SK-N-SH cells. However in SH-SY5Y cells transcription initiates further downstream and requires an alternative set of promoter elements including a +90 Ets motif. Ets2, ER81, ERM and Elk1 were identified by yeast one-hybrid selection in a human brain cDNA library using the -10 Ets motif as a bait. We have shown that ERM recognizes specifically Ets motifs on the PS1 promoter located at -10 as well as downstream at +90, +129 and +165 and activates PS1 transcription with promoter fragments whether or not they contain the -10 Ets site. We have now searched for ERM interacting proteins by yeast two-hybrid selection in a human brain cDNA library using the C-terminal 415 amino acid of ERM as a bait. One of the interacting proteins was ZNF237, a member of the MYM gene family. It is widely expressed in different tissues in eukaryotes under several forms derived by alternative splicing, including a large 382 amino acid form containing a single MYM domain, and 2 shorter forms of 208 and 213 amino acids respectively that do not. We show that both the 382 as well as the 208 amino acid forms are expressed in SK-N-SH cells but not in SH-SY5Y cells. Both forms interact with ERM and repress the transcription of PS1 in SH-SY5Y cells. The effect of both C-terminal and N-terminal deletions indicate that the Nterminal 120 amino acid region is required for interaction with ERM in yeast and furthermore single amino acid mutations show that residues 112 and 114 play an important role. The repression of transcription in SH-SY5Y cells also appears to require the N-terminal potion of ZNF237 and was affected by mutation of the amino acid 112. Data from electrophoretic mobility shift assays indicate that ERM and possibly ZNF237, interact with a fragment of the PS1 promoter.

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Section: Discussionsupporting

confidence: 78%

Analysis of transcriptional modulation of the presenilin 1 gene promoter by ZNF237, a candidate binding partner of the Ets transcription factor ERM

Pastorcic

Das

2007

Brain Research

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“…5A, B). Together, these results indicate that specific single-base differences of PEA-3 motif (G/C)AGGA(A/T)G facilitate highly selective binding of specific nuclear proteins of the large ETS super family (14,28), resulting in distinctly different functions. Namely, not all of the known PEA-3 consensus sequences and binding proteins are active in age regulation of the genes.…”

Section: Discussionmentioning

confidence: 85%

Genetic Mechanisms of Age Regulation of Protein C and Blood Coagulation

Zhang¹,

Kurachi

2002

Journal of Biological Chemistry

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Blood coagulation activity in humans increases with age. We previously identified two genetic elements, agerelated stability element (ASE; GAGGAAG) and age-related increase element (AIE; unique stretch of dinucleotide repeats), which were responsible for age-related stable and increasing expression patterns, respectively, and together recapitulated normal age regulation of the human factor IX (hFIX) gene. Here we report the ageregulatory mechanisms of human anticoagulant protein C (hPC), which shows an age-stable pattern of circulatory levels. The murine protein C gene showed an agerelated stable expression pattern in general agreement with that of the hPC. Through longitudinal analyses of transgenic mice carrying hPC minigenes, the hPC gene was found to have a functional age-related stability element (hPC ASE; CAGGAAG) in the 5-upstream proximal region but was found to lack any age-related increase element. Three other ASE-like sequences present in the hPC gene, GAGGAAA and (G/C)AGGATG, also bound nuclear proteins but were not active in the age regulation of the hPC gene. Functional hPC ASE and hFIX ASE were apparently generated through convergent evolution, and hFIX ASE can fully substitute for the hPC ASE in conferring age-related stable expression pattern of the hPC gene. In the presence of the hPC ASE, hFIX AIE can convert the age-stable expression pattern of the hPC gene to a hFIX-like age-related increase pattern. These results support the universality of ASE and AIE functions across different genes. Clearance of hPC protein from the circulation was not significantly affected by age. We now have established the basic mechanisms responsible for the age-related increase of blood coagulation activity.

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“…The employment of a yeast two-hybrid system by screening a human placenta cDNA library again yielded the same ets factor, and was designated ERT for ets-related transcription factor (Choi et al, 1998). Currently, ELF3 is the name applied to this gene (Tymms et al, 1997;Oettgen et al, 1999), based upon its belonging to the ELF (E74-like-factor) subfamily of the ets transcription factor family (Laudet et al, 1999). Its genomic organization has been elucidated and the gene localizes to human chromosome 1 q32.1 ± q32.2, a region that is altered in several tumors (Tymms et al, 1997;Oettgen et al, 1997bOettgen et al, , 1999 which may in part account for ELF3 overexpression in breast carcinogenesis (Chang et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Dual function of the epithelial specific ets transcription factor, ELF3, in modulating differentiation

et al. 2000

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The ets family of transcription factors comprises many members which contribute to diverse cellular functions that vary depending upon the cell-and tissue-type context. Recently, di erent groups have identi®ed a novel member of the ets family that is epithelial-speci®c. Variably called ESE-1, ERT, jen, ESX, this gene is designated currently as ELF3. In order to understand transcriptional regulatory mechanisms mediated by ELF3, we investigated its e ect on the human keratin 4 gene promoter based upon the role of keratin 4 in early di erentiation of the esophageal squamous epithelium. Interestingly, ELF3 suppressed basal keratin 4 promoter activity in both esophageal and cervical epithelial cancer cell lines, a novel result, while simultaneously activating the late-di erentiation linked SPRR2A promoter. Furthermore, serial deletion constructs of the keratin 4 promoter continued to be suppressed by ELF3, a phenomenon that was only partially rescued by ELF3 ets domain mutants, but completely abrogated by deletion of the ELF3 pointed domain. These results suggest that ELF3 may have dual functions in the transcriptional regulation of genes involved in squamous epithelial di erentiation. One of these functions may not be exclusively mediated through DNA binding in the context of transcriptional suppression of the keratin 4 promoter.

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Molecular phylogeny of the ETS gene family

Cited by 128 publications

References 65 publications

Analysis of transcriptional modulation of the presenilin 1 gene promoter by ZNF237, a candidate binding partner of the Ets transcription factor ERM

Analysis of transcriptional modulation of the presenilin 1 gene promoter by ZNF237, a candidate binding partner of the Ets transcription factor ERM

Genetic Mechanisms of Age Regulation of Protein C and Blood Coagulation

Dual function of the epithelial specific ets transcription factor, ELF3, in modulating differentiation

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