Identification of SCML2, a Second Human Gene Homologous to theDrosophila Sex comb on midleg(Scm): A New Gene Cluster on Xp22

Montini, Eugenio; Buchner, Georg; Spalluto, Cosma; Andolfi, Grazia; Caruso, Antonio; Dunnen, Johan T. den; Trump, Dorothy; Rocchi, Mariano; Ballabio, Andrea; Franco, Brunella

doi:10.1006/geno.1999.5755

Cited by 39 publications

(26 citation statements)

References 32 publications

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“…Interestingly, our motif appears to be restricted to mammals (FANTOM Consortium 2002). MDS00151 is a nuclearlocalization signal containing a repeat motif for the transcriptional repressor gene sex-comb on midleg-like-2 (Scml2; Montini et al 1999) and its homologs (AK016533, 6030439N15). The motif spans 24 amino acids and has two to six copies.…”

Section: Novel Domainsmentioning

confidence: 99%

Mouse Proteome Analysis

et al. 2003

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A general overview of the protein sequence set for the mouse transcriptome produced during the FANTOM2 sequencing project is presented here. We applied different algorithms to characterize protein sequences derived from a nonredundant representative protein set (RPS) and a variant protein set (VPS) of the mouse transcriptome. The functional characterization and assignment of Gene Ontology terms was done by analysis of the proteome using InterPro. The Superfamily database analyses gave a detailed structural classification according to SCOP and provide additional evidence for the functional characterization of the proteome data. The MDS database analysis revealed new domains which are not presented in existing protein domain databases. Thus the transcriptome gives us a unique source of data for the detection of new functional groups. The data obtained for the RPS and VPS sets facilitated the comparison of different patterns of protein expression. A comparison of other existing mouse and human protein sequence sets (e.g., the International Protein Index) demonstrates the common patterns in mammalian proteomes. The analysis of the membrane organization within the transcriptome of multiple eukaryotes provides valuable statistics about the distribution of secretory and transmembrane proteinsThe Mouse Gene Encyclopedia project (FANTOM Consortium 2002) provides a unique opportunity for researchers to investigate a mammalian proteome from its functional perspective. The data provide a snapshot of proteins present in the living cell and can therefore be used for functional analysis and classification.The following paper summarizes a general analysis of the mouse proteome sets deduced from the transcriptome DNA sequences based on various algorithms and approaches. We used protein domain databases, namely InterPro and Superfamily (Gough and Chothia 2002), to carry out initial functional annotation of the protein sequences and to classify these sequences according to existing biological resources, such as Gene Ontology (GO). The general coverage of proteins in the representative proteins set is about 92% for both InterPro and Superfamily, and this provides a comprehensive overview of the proteome. InterPro analysis has also been used for comparison of the different proteomes produced; this analysis highlights interesting differences between various mouse sequencing projects. New domains which are not included in existing resources have been detected using algorithms implemented in the MDS database (Kawaji et al. 2002), and seven new domain candidates have been discovered. Determination of the membrane organization within the secretory pathway, namely whether a protein is secreted into the extracellular media, a membrane-spanning protein (transmembrane protein), or a nonsecretory protein, is essential for understanding its function. This information complements other computational annotation projects, as it provides the context by determining the membrane topography of predicted functional protein units and is essential for ...

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Section: Novel Domainsmentioning

confidence: 99%

Mouse Proteome Analysis

et al. 2003

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“…The SPM domain is a self-binding protein interaction module and may mediate Scm association to Prc1 and play a key role for PcG repression, although Scm association to purified Prc1 is substoichiometric (Levine et al, 2002). In mammals, there are four paralogs for Drosophila Scm based on primary sequence: Scmh1, Scml1, Scml2 and Sfmbt (Tomotsune et al, 1999;van de Vosse et al, 1998;Montini et al, 1999;Usui et al, 2000). The mammalian Scmh1 protein has been shown to be a constituent of the mammalian Prc1 (Levine et al, 2002), which contains two highly conserved motifs, two mbt repeats in the N-terminal region and an SPM domain in the C-terminal region, that are shared with its Drosophila counterpart.…”

Section: Introductionmentioning

confidence: 99%

Mammalian Polycomb Scmh1 mediates exclusion of Polycomb complexes from the XY body in the pachytene spermatocytes

et al. 2007

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The product of the Scmh1 gene, a mammalian homolog of Drosophila Sex comb on midleg, is a constituent of the mammalian Polycomb repressive complexes 1 (Prc1). We have identified Scmh1 as an indispensable component of the Prc1. During progression through pachytene, Scmh1 was shown to be excluded from the XY body at late pachytene, together with other Prc1 components such as Phc1, Phc2, Rnf110 (Pcgf2), Bmi1 and Cbx2. We have identified the role of Scmh1 in mediating the survival of late pachytene spermatocytes. Apoptotic elimination of Scmh1 -/-spermatocytes is accompanied by the preceding failure of several specific chromatin modifications at the XY body, whereas synapsis of homologous autosomes is not affected. It is therefore suggested that Scmh1 is involved in regulating the sequential changes in chromatin modifications at the XY chromatin domain of the pachytene spermatocytes. Restoration of defects in Scmh1 -/-spermatocytes by Phc2 mutation indicates that Scmh1 exerts its molecular functions via its interaction with Prc1. Therefore, for the first time, we are able to indicate a functional involvement of Prc1 during the meiotic prophase of male germ cells and a regulatory role of Scmh1 for Prc1, which involves sex chromosomes.

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“…S1) and humans (1), nine genes encoding for proteins with MBT domains are known. Two of them, Scmh1 (25) and Scml2 (26), resemble Drosophila scm in that they contain two MBT domains and a C-terminal sterile ␣-motif (SAM) domain. Three genes, L3mbtl1 (27), L3mbtl3 (also designated MBT-1 (28)), and L3mbtl4 (supplemental Fig.…”

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confidence: 99%

Chromatin Protein L3MBTL1 Is Dispensable for Development and Tumor Suppression in Mice

Qin

Buren

Huang

et al. 2010

Journal of Biological Chemistry

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L3MBTL1, a paralogue of Drosophila tumor suppressor lethal(3)malignant brain tumor (l(3)mbt), binds histones in a methylation state-dependent manner and contributes to higher order chromatin structure and transcriptional repression. It is the founding member of a family of MBT domain-containing proteins that has three members in Drosophila and nine in mice and humans. Knockdown experiments in cell lines suggested that L3MBTL1 has non-redundant roles in the suppression of oncogene expression. We generated a mutant mouse strain that lacks exons 13-20 of L3mbtl1. Markedly reduced levels of a mutant mRNA with an out-of-frame fusion of exons 12 and 21 were expressed, but a mutant protein was undetectable by Western blot analysis. L3MBTL1 ؊/؊ mice developed and reproduced normally.The highest expression of L3MBTL1 was detected in the brain, but its disruption did not affect brain development, spontaneous movement, and motor coordination. Despite previous implications of L3mbtl1 in the biology of hematopoietic transcriptional regulators, lack of L3MBTL1 did not result in deficiencies in lymphopoiesis or hematopoiesis. In contrast with its demonstrated biochemical activities, embryonic stem (ES) cells lacking L3MBTL1 displayed no abnormalities in H4 lysine 20 (H4K20) mono-, di-, or trimethylation; had normal global chromatin density as assessed by micrococcal nuclease digests; and expressed normal levels of c-myc. Embryonic fibroblasts lacking L3MBTL1 displayed unaltered cell cycle arrest and down-regulation of cyclin E expression after irradiation. In cohorts of mice followed for more than 2 years, lack of L3MBTL1 did not alter normal lifespan or survival with or without sublethal irradiation.Proteins containing malignant brain tumor (MBT) 3 domains have recently attracted considerable attention because of their emerging role in modulating the organization of cellular DNA in aggregated nucleosomes and chromatin and their important roles in development (1-6). Similar to their better known distant relatives, chromo-and tudor domains, these protein modules selectively bind histone tails depending on the degree of methylation at specific lysine residues (7,8). MBT domains are highly conserved from Drosophila to mammals, comprise ϳ100 amino acid residues, and the structure of multiple family members has been resolved at the atomic level (2, 3, 6, 9 -13). Characteristically, MBT domains recognize mono-and dimethylated lysine residues in histone tails but not non-or trimethylated lysines (2-4, 7, 14). Human L3MBTL1, a transcriptional repressor and suspected tumor suppressor gene (15-17), was shown to be capable of compacting nucleosomal arrays by binding mono-and dimethylated histone H4K20 and histone H1bK26 in vitro (4). Thus, MBT domain proteins contribute to the complex organization of chromatin as "readers" and "effectors" of a network of post-translational histone modifications that is critical for the establishment of specific cellular differentiation states (18 -20).MBT domains were first recognized in the cloned gene ...

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Identification of SCML2, a Second Human Gene Homologous to theDrosophila Sex comb on midleg(Scm): A New Gene Cluster on Xp22

Cited by 39 publications

References 32 publications

Mouse Proteome Analysis

Mouse Proteome Analysis

Mammalian Polycomb Scmh1 mediates exclusion of Polycomb complexes from the XY body in the pachytene spermatocytes

Chromatin Protein L3MBTL1 Is Dispensable for Development and Tumor Suppression in Mice

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