TRIM24 mediates the interaction of the retinoic acid receptor alpha with the proteasome

The nuclear retinoic acid (RA) receptors (RARalpha, beta and gamma) are ligand-dependent regulators of transcription. Upon activation by RA, they are recruited at the promoters of target genes together with several coregulators. Then, they are degraded by the ubiquitin proteasome system. Here, we report that the degradation of the RARalpha subtype involves ubiquitination and the tripartite motif protein TRIM24, which was originally identified as a ligand-dependent corepressor of RARalpha. We show that in response to RA, TRIM24 serves as an adapter linking RARalpha to the proteasome for its degradation. In addition, TRIM24 and the proteasome are recruited with RARalpha to the promoters of target genes and thus are inherently linked to RARalpha transcriptional activity

TRIM

The nuclear retinoic acid (RA) receptors (RARalpha, beta and gamma) are ligand-dependent regulators of transcription. Upon activation by RA, they are recruited at the promoters of target genes together with several coregulators. Then, they are degraded by the ubiquitin proteasome system. Here, we report that the degradation of the RARalpha subtype involves ubiquitination and the tripartite motif protein TRIM24, which was originally identified as a ligand-dependent corepressor of RARalpha. We show that in response to RA, TRIM24 serves as an adapter linking RARalpha to the proteasome for its degradation. In addition, TRIM24 and the proteasome are recruited with RARalpha to the promoters of target genes and thus are inherently linked to RARalpha transcriptional activity

Genetic assignment of Tunisian meat sheep breeds and the effect of the reduction of microsatellites number on their structure assessment

Microsatellite markers succeeded to reveal different population genetic parameters. The present work aimed to investigate the genetic assignment and structure of the Tunisian meat sheep breeds. (Barbarin (BB), Western Thin Tail (WTT), and Black Thibar (BT)).The current study also opted for testing different methods of assignment implemented in several programs for genetic identification and traceability purposes of these breeds and for assessing whether these markers could be useful for an efficient genetic assignment of these ovine breeds. The genotypes of 90 animals (30 samples per breed) were typed for 22 microsatellite markers. All the loci displayed a high polymorphic content (between 0.561 and 0.884). The GENECLASS2 and the WHICHLOCI programs were used to choose the most powerful markers (17 microsatellites). The FLOCK program was more efficient with 22 markers. Genetic differentiation tests (FST = 0.0127) and assignment of individuals to populations revealed the highest level of misassignment in BB and WTT breeds, while the BT breed revealed the highest percentage of individuals assigned to itself. The reduction of the number of microsatellites (from 22 to 17) does not affect the assessment of the genetic structure of Tunisian sheep breeds. This result shed the light on the importance of the shift towards lambs with thin tails imposed by the butchers. It also revealed the unfitness of microsatellite markers in genetic identification analysis for studied sheep breeds.Publishe

Genes involved in cell adhesion and signaling: a new repertoire of retinoic acid receptor target genes in mouse embryonic fibroblasts

Nuclear retinoic acid (RA) receptors (RARalpha, beta and gamma) are ligand-dependent transcription factors that regulate the expression of a battery of genes involved in cell differentiation and proliferation. They are also phosphoproteins and we previously showed the importance of their phosphorylation in their transcriptional activity. In the study reported here, we conducted a genome-wide analysis of the genes that are regulated by RARs in mouse embryonic fibroblasts (MEFs) by comparing wild-type MEFs to MEFs lacking the three RARs. We found that in the absence of RA, RARs control the expression of several gene transcripts associated with cell adhesion. Consequently the knockout MEFs are unable to adhere and to spread on substrates and they display a disrupted network of actin filaments, compared with the WT cells. In contrast, in the presence of the ligand, RARs control the expression of other genes involved in signaling and in RA metabolism. Taking advantage of rescue cell lines expressing the RARalpha or RARgamma subtypes (either wild-type or mutated at the N-terminal phosphorylation sites) in the null background, we found that the expression of RA-target genes can be controlled either by a specific single RAR or by a combination of RAR isotypes, depending on the gene. We also selected genes that require the phosphorylation of the receptors for their regulation by RA. Our results increase the repertoire of genes that are regulated by RARs and highlight the complexity and diversity of the transcriptional programs regulated by RARs, depending on the gene

Admixture and local breed marginalization threaten Algerian sheep diversity

Due to its geo-climatic conditions, Algeria represents a biodiversity hotspot, with sheep breeds well adapted to a patchwork of extremely heterogeneous harsh habitats. The importance of this peculiar genetic reservoir increases as climate change drives the demand for new adaptations. However, the expansion of a single breed (Ouled-Djellal) which occurred in the last decades has generated a critical situation for the other breeds; some of them are being subjected to uncontrolled cross-breeding with the favored breed and/or to marginalization (effective size contraction). This study investigated genetic diversity within and among six of the nine Algerian breeds, by use of 30 microsatellite markers. Our results showed that, in spite of the census contraction experienced by most of the considered breeds, genetic diversity is still substantial (average gene diversity ranging 0.68 to 0.76) and inbreeding was not identified as a problem. However, two breeds (Rembi and Taadmit) appeared to have lost most of their genetic originality because of intensive cross-breeding with Ouled-Djellal. Based on the above evidence, we suggest Hamra, Sidaoun, and D'man as breeds deserving the highest priority for conservation in Algeria

Analysis of differences in prion protein gene (PRNP) polymorphisms between Algerian and Southern Italy's goats

Goats are adapted to live in harsh areas of the world ensuring minimum levels of milk and meat production without much economic input. Scrapie is a fatal prion disease of small ruminants detected in different countries worldwide. Polymorphisms in the prion protein gene (PRNP) modify the degree of susceptibility/resistance to scrapie. PRNP polymorphisms were analysed in the four main Algerian goat breeds (Naine de Kabylie, Arbia, Mozabite, Mekatia), and in two native breeds of South Italy (Aspromontana from Calabria and Cilentana from Campania). The results were compared also with two previously described Sicilian native breeds (Girgentana and Rossa Mediterranea). Seven amino acid substitutions were detected in Naine de Kabylie goat which represents the original native Berber breed. All other breeds presented no more than six variants and common polymorphisms were present at codons, 154 and 240. Isoleucine at 137 was present in Algerian breeds only. The Italian Cilentana shared more variants with Algerian breeds whereas the Aspromontana breed was the only one to show a Serine at 127. Exclusive new variants were not detected since all polymorphisms were already described in other goats worldwide. The scrapie protective allele encoding lysine (K) at codon 222 was detected in the Naine de Kabylie and M’zabite breeds at low-frequency whereas is present with frequencies higher than 10% in all the Italian breeds reared in regions with elevated scrapie incidence. The overall results showed a substantial number of polymorphisms in PRNP, particularly in Naine de Kabylie breed, which carried also unique genotypes

Pair-wise F_ST among Algerian breeds (a) and Italian breeds (b), calculated with a common set of 15 microsatellites^* (with confidence intervals at 95%).

<p>Ba, Bagnolese; Co, Comisana; Ge, Gentile Di Puglia; La, Laticauda; Le, Leccese; Sa, Sarda.</p><p>*the common set of microsatellites was: MAF65, MAF214, OARFCB304, ILST11, OARAE129, OARFCB193, MAF209, OARJMP58, ILST5, OARFCB128, INRA63, BM1824, MAF33, MCM140, BM8125.</p><p>Pair-wise F_ST among Algerian breeds (a) and Italian breeds (b), calculated with a common set of 15 microsatellites^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122667#t003fn002" target="_blank">*</a>} (with confidence intervals at 95%).</p

Scatterplot of the first two principal components of DAPC using breeds as prior clusters.

<p>Breeds are labeled inside their 95% inertia ellipses and dots represent individuals. The inset indicates the eigenvalues of the first five principal components.</p

Pair-wise F_ST among Algerian breeds (with confidence intervals at 95%).

<p>Pair-wise F_ST among Algerian breeds (with confidence intervals at 95%).</p