Identification of histone modifications in biomedical text for supporting epigenomic research

Corinna K, Klinger R, Hofmann-Apitius M. Identification of Histone Modifications in Biomedical Text for Supporting Epigenomic Research. BMC Bioinformatics. 2009;10(Suppl 1):S28

Physiological effects of KDM5C on neural crest migration and eye formation during vertebrate development

Background: Lysine-specific histone demethylase 5C (KDM5C) belongs to the jumonji family of demethylases and is specific for the di- and tri-demethylation of lysine 4 residues on histone 3 (H3K4 me2/3). KDM5C is expressed in the brain and skeletal muscles of humans and is associated with various biologically significant processes. KDM5C is known to be associated with X-linked mental retardation and is also involved in the development of cancer. However, the developmental significance of KDM5C has not been explored yet. In the present study, we investigated the physiological roles of KDM5C during Xenopus laevis embryonic development. Results: Loss-of-function analysis using kdm5c antisense morpholino oligonucleotides indicated that kdm5c knockdown led to small-sized heads, reduced cartilage size, and malformed eyes (i.e., small-sized and deformed eyes). Molecular analyses of KDM5C functional roles using whole-mount in situ hybridization, -galactosidase staining, and reverse transcription-polymerase chain reaction revealed that loss of kdm5c resulted in reduced expression levels of neural crest specifiers and genes involved in eye development. Furthermore, transcriptome analysis indicated the significance of KDM5C in morphogenesis and organogenesis. Conclusion: Our findings indicated that KDM5C is associated with embryonic development and provided additional information regarding the complex and dynamic gene network that regulates neural crest formation and eye development. This study emphasizes the functional significance of KDM5C in Xenopus embryogenesis; however, further analysis is needed to explore the interactions of KDM5C with specific developmental genes

Association between socioeconomic markers and adult telomere length differs according to sex: Pro-Saúde study.

Understanding the social determinants of telomere length is critical to evaluate the risk of early biological aging. We investigated sex differences on the association between socioeconomic status (SES) and demographic markers and leukocyte telomere length (LTL) in Brazilian adults. This cross-sectional study was conducted in a subsample (women=228; men=200) nested within the Pro-Saúde study, a prospective cohort study of university civil servants in Rio de Janeiro, Brazil (2012-2013). Adjusted multivariate models were used to test the relationship between SES markers (marital status, educational attainment, father's educational attainment, race/skin color, household income, and childhood experience of food deprivation) and LTL. After adjusting for age and potential health-related confounders, lower educational attainment was associated with shorter LTL among men (β=-0.05, 95% confidence interval (CI)=95%CI: -0.10, 0.00, P=0.03). In women, LTL was inversely associated with unmarried status (β=-0.05, 95%CI: -0.09, 0.00, P=0.03), lower father's educational attainment (β=-0.05, 95%CI: -0.13, 0.00, P=0.04), and childhood experience of food deprivation (β=-0.07, 95%CI: -0.13, 0.00, P=0.04). Our findings suggested that the association between SES markers and LTL differs according to sex. SES markers able to induce lifelong stress, reflected in LTL, appeared to be more related to individual factors in men, whereas in women they were family-related

Association between socioeconomic markers and adult telomere length differs according to sex: Pro-Saúde study.

Understanding the social determinants of telomere length is critical to evaluate the risk of early biological aging. We investigated sex differences on the association between socioeconomic status (SES) and demographic markers and leukocyte telomere length (LTL) in Brazilian adults. This cross-sectional study was conducted in a subsample (women=228; men=200) nested within the Pro-Saúde study, a prospective cohort study of university civil servants in Rio de Janeiro, Brazil (2012-2013). Adjusted multivariate models were used to test the relationship between SES markers (marital status, educational attainment, father's educational attainment, race/skin color, household income, and childhood experience of food deprivation) and LTL. After adjusting for age and potential health-related confounders, lower educational attainment was associated with shorter LTL among men (β=-0.05, 95% confidence interval (CI)=95%CI: -0.10, 0.00, P=0.03). In women, LTL was inversely associated with unmarried status (β=-0.05, 95%CI: -0.09, 0.00, P=0.03), lower father's educational attainment (β=-0.05, 95%CI: -0.13, 0.00, P=0.04), and childhood experience of food deprivation (β=-0.07, 95%CI: -0.13, 0.00, P=0.04). Our findings suggested that the association between SES markers and LTL differs according to sex. SES markers able to induce lifelong stress, reflected in LTL, appeared to be more related to individual factors in men, whereas in women they were family-related

Regulation of oocyte-specific chromatin organisation during prophase I by the histone demethylase Kdm5/Lid and other proteins

In Drosophila oocytes, chromosomes undergo dynamic reorganisation during the prophase of the first meiotic division. This is essential to prepare chromatin for synapsis, recombination and consequent chromosome segregation. The progression of meiotic prophase I is well described, while the molecular mechanisms and regulation of these dramatic chromosomal reorganisations are not well understood. Histone modifying enzymes are major regulators of chromatin structure, however, our knowledge of their roles in meiotic prophase I is still limited. In this work, I investigated the role of the histone demethylase Kdm5/Lid, which removes one of the trimethyl groups at Lys4 of Histone 3 (H3K4me3). I showed that Kdm5/Lid is important for the assembly of the synaptonemal complex, pairing of homologous centromeres, and the karyosome formation. Additionally, Kdm5/Lid promotes crossing over and therefore ensures accurate chromosome segregation. Although loss of Kdm5/Lid dramatically increased the level of H3K4me3 in oocytes, catalytically inactive Kdm5/Lid rescued the above cytological defects. Thereby, I found that Kdm5/Lid regulates chromatin architecture in meiotic prophase I oocytes independently of its demethylase activity. To further identify the regulators of meiotic chromatin organisation during prophase I, I carried out a small-scale RNAi screen for karyosome defects. I found that depletion of ubiquitin ligase components, SkpA, Cul-3 and Ubc-6, disrupted the karyosome formation and the assembly of the synaptonemal complex. The success of the small-scale screen motivated me to initiate the genome-scale RNAi screen for karyosome defects. I found 40 new genes that, when depleted, strongly impaired karyosome morphology. Further studies are required to confirm and elucidate their role in chromatin organisation in oocytes. Overall, my findings have advanced our understanding of the regulation of chromatin reorganisation during oocyte development. Because of the conservation between Drosophila and human meiosis, this study provides novel insights into the regulation of meiotic progression in human oocytes