693 research outputs found

    Cfp1 integrates both CpG content and gene activity for accurate H3K4me3 deposition in embryonic stem cells

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    Trimethylation of histone H3 Lys 4 (H3K4me3) is a mark of active and poised promoters. The Set1 complex is responsible for most somatic H3K4me3 and contains the conserved subunit CxxC finger protein 1 (Cfp1), which binds to unmethylated CpGs and links H3K4me3 with CpG islands (CGIs). Here we report that Cfp1 plays unanticipated roles in organizing genome-wide H3K4me3 in embryonic stem cells. Cfp1 deficiency caused two contrasting phenotypes: drastic loss of H3K4me3 at expressed CGI-associated genes, with minimal consequences for transcription, and creation of “ectopic” H3K4me3 peaks at numerous regulatory regions. DNA binding by Cfp1 was dispensable for targeting H3K4me3 to active genes but was required to prevent ectopic H3K4me3 peaks. The presence of ectopic peaks at enhancers often coincided with increased expression of nearby genes. This suggests that CpG targeting prevents “leakage” of H3K4me3 to inappropriate chromatin compartments. Our results demonstrate that Cfp1 is a specificity factor that integrates multiple signals, including promoter CpG content and gene activity, to regulate genome-wide patterns of H3K4me3

    Chromatin Folding and Nuclear Architecture: PRC1 Function in 3D

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    Embryonic development requires the intricate balance between the expansion and specialisation of defined cell types in time and space. The gene expressionprogrammes that underpin this balance are regulated, in part, by modulating thechemical and structural state of chromatin. Polycomb repressive complexes (PRCs), a family of essential developmental regulators, operate at this level to stabilise or perpetuate a repressed but transcriptionally poised chromatin configuration. This dynamic state is required to control the timely initiation of productive gene transcription during embryonic development. The two major PRCs cooperate to target the genome, but it is PRC1 that appears to be the primary effector that controls gene expression. In this review I will discuss recent findings relating to how PRC1 alters chromatin accessibility, folding and global 3D nuclear organisation to control gene transcription

    Comprehensive analysis of human CpG island methylation

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    The Hubble Space Telescope Extragalactic Distance Scale Key Project. X. The Cepheid Distance to NGC 7331

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    The distance to NGC 7331 has been derived from Cepheid variables observed with HST/WFPC2, as part of the Extragalactic Distance Scale Key Project. Multi-epoch exposures in F555W (V) and F814W (I), with photometry derived independently from DoPHOT and DAOPHOT/ALLFRAME programs, were used to detect a total of 13 reliable Cepheids, with periods between 11 and 42 days. The relative distance moduli between NGC 7331 and the LMC, imply an extinction to NGC 7331 of A_V = 0.47+-0.15 mag, and an extinction-corrected distance modulus to NGC 7331 of 30.89+-0.14(random) mag, equivalent to a distance of 15.1 Mpc. There are additional systematic uncertainties in the distance modulus of +-0.12 mag due to the calibration of the Cepheid Period-Luminosity relation, and a systematic offset of +0.05+-0.04 mag if we applied the metallicity correction inferred from the M101 results of Kennicutt et al 1998.Comment: To be published in The Astrophysical Journal, 1998 July 1, v501 note: Figs 1 and 2 (JPEG files) and Fig 7 (multipage .eps file) need to be viewed/printed separatel

    The Sextet Arcs: a Strongly Lensed Lyman Break Galaxy in the ACS Spectroscopic Galaxy Survey towards Abell 1689

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    We present results of the HST Advanced Camera for Surveys spectroscopic ground-based redshift survey in the field of A1689. We measure 98 redshifts, increasing the number of spectroscopically confirmed objects by sixfold. We present two spectra from this catalog of the Sextet Arcs, images which arise from a strongly-lensed Lyman Break Galaxy (LBG) at a redshift of z=3.038. Gravitational lensing by the cluster magnifies its flux by a factor of ~16 and produces six separate images with a total r-band magnitude of r_625=21.7. The two spectra, each of which represents emission from different regions of the LBG, show H I and interstellar metal absorption lines at the systemic redshift. Significant variations are seen in Ly-alpha profile across a single galaxy, ranging from strong absorption to a combination of emission plus absorption. A spectrum of a third image close to the brightest arc shows Ly-alpha emission at the same redshift as the LBG, arising from either another spatially distinct region of the galaxy, or from a companion galaxy close to the LBG. Taken as a group, the Ly-alpha equivalent width in these three spectra decreases with increasing equivalent width of the strongest interstellar absorption lines. We discuss how these variations can be used to understand the physical conditions in the LBG. Intrinsically, this LBG is faint, ~0.1L*, and forming stars at a modest rate, ~4 solar masses per year. We also detect absorption line systems toward the Sextet Arcs at z=2.873 and z=2.534. The latter system is seen across two of our spectra.Comment: Accepted for publication in Ap
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