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Background. Rosacea is a chronic skin disease, possibly following the neurogenic skin inflammation model. Neurokinin B, involved in the pathogenesis of Parkinson's disease, frequently coexisting with subsequent onset of rosacea, is an endogenous ligand of the tachykinin receptor 3 (TACR3). Methods. 128 rosacea patients and 121 matched controls were genotyped for rs3733631 by PCR-RFLP and analyzed by chi-square test. Results. We observed statistically significant predominance of the C/G or G/G genotype (p = 0.006) and of the G allele (p = 0.004) in the papulopustular (PP) form of rosacea and statistically marginal significance of the C/G or G/G genotype in erythematotelangiectatic (ET) rosacea (p = 0.052). Significantly higher frequency of the C/G or G/G genotype and G allele in PP rosacea (p = 0.021 and p = 0.008, resp.) was ascertained within male patients. Conclusion. TACR3 rs3733631 G allele possibly predisposes the evolution of the initial phase of rosacea to the PP and not the ET form in male patients.

Objective: The aims of this study were to evaluate the impact of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on several psychological characteristics in a group of Greek University students and to explore putative interactions with the serotonin-transporter-linked polymorphic region (5-HTTLPR) and serious past adverse experiences., Methods: A total of 224 students were genotyped and classified as (a) carriers or noncarriers of the Met allele of the BDNF Val66Met polymorphism and (b) carriers or noncarriers of the S or Lg alleles (S') of the 5-HTTLPR polymorphism. Students were evaluated using a battery of standard psychological tests and answered questionnaires on serious past adverse experiences., Results: The Val/Val BDNF genotype was associated with higher scores in several psychopathological dimensions. When the effect of the BDNF Met allele was examined in relation to 5-HTTLPR, it was restricted to S' noncarriers. Among these students, BDNF Met allele carriers had lower scores compared with noncarriers. The effects of the Met allele on the S' allele noncarriers in the anxiety and phobic anxiety dimensions were more pronounced among individuals who had reported no serious life adversities., Conclusion: There may be a protective role of the BDNF Met allele in several psychopathological features and it is suggested that some of these effects are moderated by 5-HTTLPR.

Background: Evidence suggests that Notch gene aberrations may be involved in the clinical expression of psoriasis. There are reports of Notch2 receptor expression peculiarities in psoriatic skin and others, indicating that VEGF-induced Notch4 overexpression promotes endothelial cell morphology alterations and that increased dermis vessel permeability histogenetically precedes the development of psoriatic lesions., Objective: To investigate the correlation of polymorphisms in Notch2 and Notch4 genes with the appearance of psoriasis vulgaris., Material and Methods: Up to 305 patients suffering from psoriasis vulgaris were included in the study, genotyped by either real time quantitative PCR or PCR-RFLP., Results: We observed: (a) Notch2: Statistically significant predominance of T/C genotype in male patients (p=0.037); (b) Notch4: Significantly higher frequency of the SNP1 T/T genotype (p=0.039) in psoriatic females; significant predominance of the SNP2 G/G and A/G (p=0.014) genotypes in female patients with late onset psoriasis (p=0.001)., Conclusion: This study supports the involvement of both Notch2 and Notch4 in the pathogenesis of psoriasis vulgaris. Pathogenetic participation of Notch2 seems more evident in male patients, possibly early onset, while that of Notch4 is more evident in late onset female patients.

Aim: To study the effect of the serotonin transporting gene L/S polymorphism on several psychological characteristics in a group of Greek University students., Methods: One hundred eighty-one students were genotyped and classified into two groups: carriers or noncarriers of an S allele. Students were evaluated with a battery of psychological tests (Zung depression rating scale, symptoms check-list-90-R, Eysenck personality inventory); they also answered questionnaires regarding serious past adverse experiences as well as nicotine and alcohol use. Multivariate analysis of variance (MANOVA) was used to check the main effect of genotype and its interaction with both adverse life experiences and scores of psychological tests., Results: No significant differences were detected between the two groups of students regarding scores of the psychological tests. Yet, analysis with MANOVA indicated an interaction between genotype and adversities (lambda = 0.838, F(17,158) = 1.802, P = 0.032). Students who both carry at least one S allele and have faced serious past adverse life experiences have scored higher than carriers of the S allele who have not faced adversities on the following: global severity index (F(1174) = 5.973, P = 0.016), positive symptoms distress index (F(1174) = 4.518, P = 0.035), somatization (F(1174) = 4.074, P = 0.045), depression (F(1174) = 4.971, P = 0.027), anxiety (F(1174) = 8.112, P = 0.005), phobic anxiety (F(1174) = 16.421, P < 0.000), and paranoid ideation (F(1174) = 5.143, P = 0.025). Among students without adversities, those with the LL genotype have scored higher than S allele carriers on the following: depression (t = 2.680, df = 75, P = 0.009), anxiety (t = 2.629, df = 75, P = 0.010), phobic anxiety (t = 3.350, df = 75, P = 0.001), and paranoid ideation (t = 2.668, df = 75, P = 0.009)., Conclusion: The S and L alleles seem to interact differently with serious past life adversities in influencing psychological vulnerability. Adversities seem to have a stronger effect on S carriers. LL genotype might be related to the expression of certain more endogenous psychopathological tendencies., ((c) 2008 Wiley-Liss, Inc.)

We have examined HP1beta-chromatin interactions in different molecular contexts in vitro and in vivo. Employing purified components we show that HP1beta exhibits selective, stoichiometric, and salt-resistant binding to recombinant histone H3, associating primarily with the helical "histone fold" domain. Furthermore, using "bulk" nucleosomes released by MNase digestion, S-phase extracts, and fragments of peripheral heterochromatin, we demonstrate that HP1beta associates more tightly with destabilized or disrupted nucleosomes (H3/H4 subcomplexes) than with intact particles. Western blotting and mass spectrometry data indicate that HP1beta-selected H3/H4 particles and subparticles possess a complex pattern of posttranslational modifications but are not particularly enriched in me3K9-H3. Consistent with these results, mapping of HP1beta and me3K9-H3 sites in vivo reveals overlapping, yet spatially distinct patterns, while transient transfection assays with synchronized cells show that stable incorporation of HP1beta-gfp into heterochromatin requires passage through the S-phase. The data amassed challenge the dogma that me3K9H3 is necessary and sufficient for HP1 binding and unveil a new mode of HP1-chromatin interactions.

We developed a model system whereby HP1 can be targeted to pericentric heterochromatin in ES cells lacking Suv(3)9h1/2 histone methyltransferase (HMTase) activities. HP1 so targeted can reconstitute tri-methylated lysine 9 of histone H3 (Me(3)K9H3) and tri-methylated lysine 20 of histone H4 (Me(3)K20H4) at pericentric heterochromatin, indicating that HP1 can regulate the distribution of these histone modifications in vivo. Both homo- and hetero-typic interactions between the HP1 isotypes were demonstrated in vivo as were HP1 interactions with the ESET/SETDB1 HMTase and the ATRX chromatin remodelling enzyme. We conclude that HP1 not only "deciphers" the histone code but can also "encode it".

Using heterochromatin-enriched fractions, we have detected specific binding of mononucleosomes to the N-terminal domain of the inner nuclear membrane protein lamin B receptor. Mass spectrometric analysis reveals that LBR-associated particles contain complex patterns of methylated/acetylated histones and are devoid of "euchromatic" epigenetic marks. LBR binds heterochromatin as a higher oligomer and forms distinct nuclear envelope microdomains in vivo. The organization of these membrane assemblies is affected significantly in heterozygous ic (ichthyosis) mutants, resulting in a variety of structural abnormalities and nuclear defects.

Tri-methylated lysine 20 on histone H4 (Me(3)K20H4) is a marker of constitutive heterochromatin in murine interphase and metaphase cells. Heterochromatin marked by Me(3)K20H4 replicates late during S phase of the cell cycle. Serum starvation increases the number of cells that exhibit high levels of Me(3)K20H4 at constitutive heterochromatin. Me(3)K20H4 is also present at the centromeric heterochromatin of most meiotic chromosomes during spermatogenesis and at the pseudoautosomal region, as well as at some telomeres. It is not present on the XY-body. During murine embryogenesis the maternal pronucleus contains Me(3)K20H4; Me(3)K20H4 is absent from the paternal pronucleus. On Drosophila polytene chromosomes Me(3)K20H4 is present in a 'punctate pattern' at many chromosomal bands, including the chromocenter. In coccids it is present on the facultatively heterochromatinised paternal chromosome set. We also present evidence that Me(3)K20H4 is dependent upon H3-specific Suv(3)9 histone methyltransferase activity, suggesting that there may be 'epigenetic cross-talk' between histones H3 and H4.

Nuclear envelope-peripheral heterochromatin fractions contain multiple histone kinase activities. In vitro assays and amino-terminal sequencing show that one of these activities co-isolates with heterochromatin protein 1 (HP1) and phosphorylates histone H3 at threonine 3. Antibodies recognizing this post-translational modification reveal that in vivo phosphorylation at threonine 3 commences at early prophase in the vicinity of the nuclear envelope, spreads to pericentromeric chromatin during prometaphase and is fully reversed by late anaphase. This spatio-temporal pattern is distinct from H3 phosphorylation at serine 10, which also occurs during cell division, suggesting segregation of differentially phosphorylated chromatin to different regions of mitotic chromosomes.

We have recently shown that heterochromatin protein 1 (HP1) interacts with the nuclear envelope in an acetylation-dependent manner. Using purified components and in vitro assays, we now demonstrate that HP1 forms a quaternary complex with the inner nuclear membrane protein LBR and a sub-set of core histones. This complex involves histone H3/H4 oligomers, which mediate binding of LBR to HP1 and cross-link these two proteins that do not interact directly with each other. Consistent with previous observations, HP1 and LBR binding to core histones is strongly inhibited when H3/H4 are modified by recombinant CREB-binding protein, revealing a new mechanism for anchoring domains of under-acetylated chromatin to the inner nuclear membrane.