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  • 1
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    Suboptimization of developmental enhancers (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-10-17
    Description: Transcriptional enhancers direct precise on-off patterns of gene expression during development. To explore the basis for this precision, we conducted a high-throughput analysis of the Otx-a enhancer, which mediates expression in the neural plate of Ciona embryos in response to fibroblast growth factor (FGF) signaling and a localized GATA determinant. We provide evidence that enhancer specificity depends on submaximal recognition motifs having reduced binding affinities ("suboptimization"). Native GATA and ETS (FGF) binding sites contain imperfect matches to consensus motifs. Perfect matches mediate robust but ectopic patterns of gene expression. The native sites are not arranged at optimal intervals, and subtle changes in their spacing alter enhancer activity. Multiple tiers of enhancer suboptimization produce specific, but weak, patterns of expression, and we suggest that clusters of weak enhancers, including certain "superenhancers," circumvent this trade-off in specificity and activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farley, Emma K -- Olson, Katrina M -- Zhang, Wei -- Brandt, Alexander J -- Rokhsar, Daniel S -- Levine, Michael S -- GM46638/GM/NIGMS NIH HHS/ -- NS076542/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):325-8. doi: 10.1126/science.aac6948.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. msl2@princeton.edu ekfarley@princeton.edu. ; Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. ; Department of Medicine, University of California, San Diego, CA 92093-0688, USA. ; Department of Chemistry, University of California, Berkeley, CA 94720-3200, USA. ; Department of Molecular and Cell Biology, Division of Genetics, Genomics and Development, Center for Integrative Genomics, University of California, Berkeley, CA 94720-3200, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472909" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Ciona intestinalis/genetics/*growth & development ; Consensus Sequence ; Enhancer Elements, Genetic/genetics/*physiology ; Fas-Associated Death Domain Protein/metabolism ; Fibroblast Growth Factors/*metabolism ; GATA Transcription Factors/*metabolism ; *Gene Expression Regulation, Developmental ; Molecular Sequence Data ; Organ Specificity/genetics/physiology ; Otx Transcription Factors/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    The ionized absorber and nuclear environment of IRAS 13349+2438: multi-wavelength insights from coordinated Chandra HETGS, HST STIS, HET and Spitzer IRS (2013)
    Oxford University Press
    Details
    Publication Date: 2013-03-23
    Description: We present results from a multi-wavelength infrared (IR)-to-X-ray campaign of the infrared bright (but highly optical-ultraviolet extincted) quasi-stellar object (QSO) IRAS 13349+2438 obtained with the Chandra High Energy Transmission Grating Spectrometer (HETGS), the Hubble Space Telescope ( HST ) Space Telescope Imaging Spectrograph (STIS), the Hobby–Eberly Telescope (HET) 8 m and the Spitzer Infrared Spectrometer (IRS). Based on HET optical spectra of [O iii ], we refine the redshift of IRAS 13349 to be z  = 0.108 53. The weakness of the [O iii ] in combination with strong Fe ii in the HET spectra reveals extreme Eigenvector-1 characteristics in IRAS 13349, but the 2468 km s –1 width of the Hβ line argues against a narrow-line Seyfert 1 classification; on average, IR, optical and optical-ultraviolet (UV) spectra show IRAS 13349 to be a typical QSO. Independent estimates based on the Hβ line width and fits to the IRAS 13349 spectral energy distribution (SED) both give a black hole mass of M BH  = 10 9 M . The heavily reddened STIS UV spectra reveal for the first time blueshifted absorption from Ly α , N v and C iv , with components at systemic velocities of $-950 {{\rm km} {\rm s}^{-1}}$ and $-75 {\rm km} {\rm s}^{-1}\,$ . The higher velocity UV lines are coincident with the lower ionization ( ~ 1.6) WA-1 warm absorber lines seen in the X-rays with the HETGS. In addition, a  ~ 3.4 WA-2 is also required by the data, while a  ~ 3 WA-3 is predicted by theory and seen at less significance; all detected X-ray absorption lines are blueshifted by ~ 700-900 km s –1 . Theoretical models comparing different ionizing SEDs reveal that including the UV (i.e. the accretion disc) as part of the ionizing continuum has strong implications for the conclusions one would draw about the thermodynamic stability of the warm absorber. Specific to IRAS 13349, we find that an X-ray–UV ionizing SED favours a continuous distribution of ionization states in a smooth flow (this paper) versus discrete clouds in pressure equilibrium (previous work by other authors). Direct detections of dust are seen in both the IR and X-rays. We see weak polycyclic aromatic hydrocarbon (PAH) emission at 7.7 μm and 11.3 μm which may also be blended with forsterite, and 10 μm and 18 μm silicate emission, as well as an Fe L edge at 700 eV indicative of iron-based dust with a dust-to-gas ratio 〉90 per cent. We develop a geometrical model in which we view the nuclear regions of the QSO along a line of sight that passes through the upper atmosphere of an obscuring torus. This sight line is largely transparent in X-rays since the gas is ionized, but it is completely obscured by dust that blocks a direct view of the UV/optical emission region. In the context of our model, 20 per cent of the intrinsic UV/optical continuum is scattered into our sight line by the far wall of an obscuring torus. An additional 2.4 per cent of the direct light, which likely dominates the UV emission, is Thomson-scattered into our line of sight by another off-plane component of highly ionized gas.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    Acoel genome reveals the regulatory landscape of whole-body regeneration (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Whole-body regeneration is accompanied by complex transcriptomic changes, yet the chromatin regulatory landscapes that mediate this dynamic response remain unexplored. To decipher the regulatory logic that orchestrates regeneration, we sequenced the genome of the acoel worm 〈i〉Hofstenia miamia〈/i〉, a highly regenerative member of the sister lineage of other bilaterians. Epigenomic profiling revealed thousands of regeneration-responsive chromatin regions and identified dynamically bound transcription factor motifs, with the early growth response (EGR) binding site as the most variably accessible during 〈i〉Hofstenia〈/i〉 regeneration. Combining 〈i〉egr〈/i〉 inhibition with chromatin profiling suggests that Egr functions as a pioneer factor to directly regulate early wound-induced genes. The genetic connections inferred by this approach allowed the construction of a gene regulatory network for whole-body regeneration, enabling genomics-based comparisons of regeneration across species.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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