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A heterochromatin protein 1 homologue in Caenorhabditis elegans acts in germline and vulval development.

Author(s) : Couteau F, Guerry F, Muller F, Palladino F,
Journal : EMBO Rep
Proteins of the highly conserved heterochromatin protein 1 (HP1) family have been found to function in the dynamic organization of nuclear architecture and in gene regulation throughout the eukaryotic kingdom. In addition to being key players in heterochromatin-mediated gene silencing, HP1 proteins may also contribute to thetranscriptional repression of euchromatic genes via the recruitment to specific promoters. To investigate the role played by these different activities in specific developmental pathways, we identified HP1 homologues in the genome of Caenorhabditis elegans and used RNA-mediated interference to study their function. We show that one of the homologues, HPL-2, is required for the formation of a functional germline and for the development of the vulva by acting in an Rb-related pathway. We suggest that, by acting as repressors of gene expression, HP1 proteins may fulfil specific functions in both somatic and germline differentiation processes throughout development.

Centromeres become unstuck without heterochromatin.

Author(s) : Bernard P, Allshire R,
Journal : Trends Cell Biol
In most if not all eukaryotes, sister-chromatid cohesion, which is mediated by the chromosomal complex Cohesin, is destroyed by proteolysis at the transition from metaphase to anaphase. In metazoans, Cohesin is removed from chromosomes intwo steps, and the centromere and its associated pericentric heterochromatin constitute the last point of linkage between sister chromatids at metaphase. Mechanistic insight is now emerging on the way in which cells distinguish cohesion at the centromere from cohesion along chromosome arms. We discuss recent advances in our understanding of the role of centromeric heterochromatin in sister-chromatid cohesion and propose a causal relationship between this specialized type of chromatin and the removal by proteolysis of Cohesins that are associated with it.

Coactivator/corepressor ratios modulate PR-mediated transcription by the selective receptor modulator RU486

Author(s) : Liu Z, Auboeuf D, Wong J, Chen J, Tsai S, Tsai M, O'Malley B,
Journal : Proc Natl Acad Sci U S A

Coordinate regulation of transcription and splicing by steroid receptor coregulators

Author(s) : Auboeuf D, H?nig A, Berget S, O'Malley B,
Journal : Science

Na,K-ATPase alpha and beta subunit genes exhibit unique expression patterns during zebrafish embryogenesis.

Author(s) : Canfield V, Loppin B, Thisse B, Thisse C, Postlethwait J, Mohideen M, Rajarao S, Levenson R,
Journal : Mech Dev
We have used in situ hybridization to analyze Na,K-ATPase alpha and beta subunitgene expression during zebrafish embryogenesis. The most striking finding is that each of the 14 Na,K-ATPase genes exhibits a distinct expression profile. All alpha and beta subunit genes are expressed in the nervous system, although the pattern of expression in different regions varies dramatically. In peripheral tissues, three of the five alpha1-like genes are expressed in pronephros and mucous cells, one is expressed in heart, and one is predominant in skeletal muscle. The alpha2 gene is expressed in brain and heart but is most prominent inskeletal muscle, while the two alpha3 genes are restricted in their expression to the nervous system. Of the six beta subunit genes, beta1a is expressed at highest abundance in lens, pronephros, and heart, while beta1b transcripts are abundant in mucous cells. The two beta2-like genes are differentially expressed in the nervous system. One beta3 gene is expressed exclusively in brain while the otheris abundantly expressed in skeletal muscle. Based on these expression patterns, we predict that at least 14 alpha/beta subunit pairs are likely to be formed in different tissues.

Organizer activity of the polar cells during Drosophila oogenesis.

Author(s) : Grammont M, Irvine K,
Journal : Development
Patterning of the Drosophila egg requires the establishment of several distinct types of somatic follicle cells, as well as interactions between these follicle cells and the oocyte. The polar cells occupy the termini of the follicle and arespecified by the activation of Notch. We have investigated their role in follicle patterning by creating clones of cells mutant for the Notch modulator fringe. This genetic ablation of polar cells results in cell fate defects within surrounding follicle cells. At the anterior, the border cells, the immediately adjacent follicle cell fate, are absent, as are the more distant stretched and centripetal follicle cells. Conversely, increasing the number of polar cells by expressing an activated form of the Notch receptor increases the number of border cells. At the posterior, elimination of polar cells results in abnormal oocyte localization. Moreover, when polar cells are mislocalized laterally, the surrounding follicle cells adopt a posterior fate, the oocyte is located adjacent to them, and the anteroposterior axis of the oocyte is re-oriented with respect to the ectopic polar cells. Our observations demonstrate that the polar cells act as an organizer that patterns surrounding follicle cells and establishes the anteroposterior axis of the oocyte. The origin of asymmetry during Drosophila development can thus be traced back to the specification of the polar cells during early oogenesis.

Phosphorylation of the RNA polymerase II carboxyl-terminal domain by CDK9 is directly responsible for human immunodeficiency virus type 1 Tat-activated transcriptional elongation

Author(s) : Kim Y, Bourgeois C, Isel C, Churcher M, Karn J,
Journal : Mol Cell Biol

Properties of a chimeric simian-human immunodeficiency virus expressing an hybrid HIV-1 Nef/SIVmac Nef protein.

Author(s) : Bertsch C, Cluet D, Beyer C, Gloeckler L, Cecile A, Gut J, Aubertin A,
Journal : Arch Virol
The nef genes of human and simian immunodeficiency viruses code for a membrane associated protein critical for AIDS development. SIVmac Nef presents C-terminala 27 amino acid extension absent of HIV-1 Nef. To estimate the influence of thisC-terminal domain on virus properties, we constructed viruses derived from SIVmac239 by replacing SIV nef with HIV-1 Lai nef gene (SHIV NefLai4) or with a sequence encoding a Nef fusion protein: HIV-1 Lai Nef/SIV Nef-Cterm (SHIV-Cterm). The recombinant viruses replicated efficiently in vitro in CEMx174 cells and in activated macaque PBMCs. The addition of SIV Nef C-terminal domain to HIV-1 Nef in SHIVNefLai4 did not change the in vitro properties of the chimeric virus, both viruses being more infectious than a nef deleted virus. Although the half-life of Nef fusion protein was augmented, SHIV-Cterm remained slightly less infectious than SIVmac239.

Regulation of alternative splicing by the ATP-dependent DEAD-box RNA helicase p72

Author(s) : H?nig A, Auboeuf D, Parker M, O'Malley B, Berget S,
Journal : Mol Cell Biol

Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing premature RNA release at terminator sequences

Author(s) : Bourgeois C, Kim Y, Churcher M, West M, Karn J,
Journal : Mol Cell Biol

Strong-association-rule mining for large-scale gene-expression data analysis: a case study on human SAGE data.

Author(s) : Becquet C, Blachon S, Jeudy B, Boulicaut J, Gandrillon O,
Journal : Genome Biol
BACKGROUND: The association-rules discovery (ARD) technique has yet to be applied to gene-expression data analysis. Even in the absence of previous biological knowledge, it should identify sets of genes whose expression is correlated. The first association-rule miners appeared six years ago and proved efficient at dealing with sparse and weakly correlated data. A huge international research effort has led to new algorithms for tackling difficult contexts and these are particularly suited to analysis of large gene-expression matrices. To validate the ARD technique we have applied it to freely available human serial analysis of gene expression (SAGE) data. RESULTS: The approach described here enables us to designate sets of strong association rules. We normalized the SAGE data before applying our association rule miner. Depending on the discretization algorithm used, different properties of the data were highlighted. Both common and specific interpretations could be made from the extracted rules. In each and every case the extracted collections of rules indicated that a very strong co-regulation ofmRNA encoding ribosomal proteins occurs in the dataset. Several rules associating proteins involved in signal transduction were obtained and analyzed, some pointing to yet-unexplored directions. Furthermore, by examining a subset of these rules, we were able both to reassign a wrongly labeled tag, and to proposea function for an expressed sequence tag encoding a protein of unknown function.CONCLUSIONS: We show that ARD is a promising technique that turns out to be complementary to existing gene-expression clustering techniques.

The v-erbA oncogene blocks expression of alpha2/beta1 integrin a normal inhibitor of erythroid progenitor proliferation.

Author(s) : Mey A, Gandrillon O, McNagny K, Clegg D, Samarut J,
Journal : Oncogene
T2EC are chicken erythrocytic progenitors that balance between self-renewal and differentiation as a function of response to specific growth factors. Their transformation by the v-erbA oncogene locks them into the self-renewal program. We show here that the expression of the VLA-2 integrin alpha2 subunit mRNA is downregulated by v-erbA and that VLA-2 engagement and clustering, brought about by treatment with an alpha2-specific antibody or by culture on the VLA-2 ligand collagen I, inhibits T2EC proliferation. From competition studies using antibodies, VLA-2 was shown to be involved in the collagen-induced response. While engagement of VLA-2 inhibited proliferation, it was not sufficient to induce differentiation. The transformation of T2EC by v-erbA decreased their interaction with collagen I and the VLA-2 brake on cell proliferation, which mayaccount for the increased proliferation potential of transformed erythrocytic progenitors and for their shedding into the blood of infected chickens. Our datasuggest that the interaction between erythroid progenitors and collagen, mediated by VLA-2, play a major role in the control of erythropoiesis in vitro and that this pathway is a target of the v-erbA oncogene.

The v-erbA oncogene. Assessing its differentiation-blocking ability using normal chicken erythrocytic progenitor cells.

Author(s) : Gandrillon O,
Journal : Methods Mol Biol

Two Na,K-ATPase beta 2 subunit isoforms are differentially expressed within the central nervous system and sensory organs during zebrafish embryogenesis.

Author(s) : Rajarao J, Canfield V, Loppin B, Thisse B, Thisse C, Yan Y, Postlethwait J, Levenson R,
Journal : Dev Dyn
We have identified cDNAs encoding a second zebrafish ortholog of the human Na,K-ATPase beta 2 subunit. The beta 2b cDNA encodes a 292 amino acid-long polypeptide with 74% identity to the previously characterized zebrafish beta 2a subunit. By using a zebrafish meiotic mapping panel, we determined that the beta2b gene (atp1b2b) was tightly linked to markers on linkage group 5, whereas the beta 2a gene was located on linkage group 23. In situ hybridization analysis shows that in developing zebrafish embryos, atp1b2a and atp1b2b are predominantly expressed in the nervous system. beta 2a transcripts were abundantly expressed throughout brain as well as spinal cord neurons and lateral line ganglia. In contrast, beta 2b mRNA expression was primarily detected in sensory organs, including retina, otic vesicles, and lateral line neuromast cells. These resultssuggest that the beta 2a and beta 2b genes play distinct roles in developing brain and sensory organs, and raise the possibility that the functions encoded by the single mammalian beta 2 gene may be partitioned between the two zebrafish beta 2 orthologs.