Genes invoked in the ovarian transition to menopause

Menopause and the associated declines in ovarian function are major health issues for women. Despite the widespread health impact of this process, the molecular mechanisms underlying the aging-specific decline in ovarian function are almost completely unknown. To provide the first gene–protein analysis of the ovarian transition to menopause, we have established and contrasted RNA gene expression profiles and protein localization and content patterns in healthy young and perimenopausal mouse ovaries. We report a clear distinction in specific mRNA and protein levels that are noted prior to molecular evidence of steroidogenic failure. In this model, ovarian reproductive aging displays similarities with chronic inflammation and increased sensitivity to environmental cues. Overall, our results indicate the presence of mouse climacteric genes that are likely to be major players in aging-dependent changes in ovarian function

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

doi:10.1093/nar/gkl387 Genes invoked in the ovarian transition to menopause

Menopause and the associated declines in ovarian function are major health issues for women. Despite the widespread health impact of this process, the molecular mechanisms underlying the agingspecific decline in ovarian function are almost completely unknown. To provide the first gene– protein analysis of the ovarian transition to menopause, we have established and contrasted RNA gene expression profiles and protein localization and content patterns in healthy young and perimenopausal mouse ovaries. We report a clear distinction in specific mRNA and protein levels that are noted prior to molecular evidence of steroidogenic failure. In this model, ovarian reproductive aging displays similarities with chronic inflammation and increased sensitivity to environmental cues. Overall, our results indicate the presence of mouse climacteric genes that are likely to be major players in aging-dependent changes in ovarian function

DNA array to confirm differential gene expression in young and old ovaries

<p><b>Copyright information:</b></p><p>Taken from "Genes invoked in the ovarian transition to menopause"</p><p>Nucleic Acids Research 2006;34(11):3279-3287.</p><p>Published online 28 Jun 2006</p><p>PMCID:PMC1904106.</p><p>© 2006 The Author(s)</p> Identical DNA array membranes containing probes for 440 aging-related mouse genes were probed with individual P-labeled cDNA libraries prepared from () young and () aged ovaries. Lower panels of () and () show an enlargement of the framed membrane portions in the upper panels. Matrix overlay maps the position of the nucleotides for each gene. Positions 62, Leptin; 79, CD36 antigen; 117, unknown EST are examples of decreased levels with aging. Positions 58, peroxisome proliferators activated receptor-a; 105, transcription factor NFκB are examples of increased levels with aging

Western blots of total protein lysates from young and old mouse ovaries

<p><b>Copyright information:</b></p><p>Taken from "Genes invoked in the ovarian transition to menopause"</p><p>Nucleic Acids Research 2006;34(11):3279-3287.</p><p>Published online 28 Jun 2006</p><p>PMCID:PMC1904106.</p><p>© 2006 The Author(s)</p> () Proteins with reduced content in old (o) ovaries compared with young ovaries (y); () proteins with higher level in young ovaries; and () no change in protein content. Proteins were visualized with protein-specific antibodies as indicated at the left of the panels. The size (kDa) of the protein marker is indicated at the right of the panels. All lanes received 100 μg of total ovarian lysate. The immunological reactions are visualized by HSP-coupled secondary antibodies

In vivo DNase I-mediated footprinting analysis along the human bradykinin B1 receptor (BDKRB1) gene promoter: evidence for cell-specific regulation

By applying in vivo dimethyl sulphate and UV light type C-footprinting analysis, we previously showed that specific DNA sequences in the −1349/+42 core promoter region of the inducible human BDKRB1 (bradykinin B1 receptor) gene correlated with its transcriptional activity. In the present study we used the highly sensitive DNase I in vivo footprinting approach to delineate more precisely the functional domains of the BDKRB1 gene promoter in human SMCs (smooth muscle cells). Human lymphocytes that do not express a functional BDKRB1 were also studied as a reference using dimethyl sulphate, UV light type C and DNase I treatments. An obvious difference was found in the DNase I-footprinting patterns between cellular systems that express a functional BDKRB1 (SMCs) in comparison with human lymphocytes, where randomly distributed nucleosome-like footprinting patterns were found in the bulk of the core promoter region studied. Gel-shift assays and expression studies pointed to the implication of the YY1 and a TBP/TFIIB (TATA-box-binding protein/transcription factor IIB) transcription factor in the regulation of BDKRB1 gene expression in SMCs and possible YY1 involvement in the mechanisms of nuclear factor κB-mediated regulation of the receptor expression. No significant changes in the promoter foot-printing pattern were found after treatment with interleukin-1β or serum (known BDKRB1 gene inducers), indicating that definite regulatory motifs could exist outside the BDKRB1 gene core promoter region studied