Recent CIG publications Archive

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Genome Res.: auth.: group Kaessmann

Genome Res. 2017 Nov 13. doi: 10.1101/gr.223727.117. [Epub ahead of print]

Convergent origination of a Drosophila-like dosage compensation mechanism in a reptile lineage.

Abstract

Sex chromosomes differentiated from different ancestral autosomes in various vertebrate lineages. Here, we trace the functional evolution of the XY Chromosomes of the green anole lizard (Anolis carolinensis), on the basis of extensive high-throughput genome, transcriptome and histone modification sequencing data and revisit dosage compensation evolution in representative mammals and birds with substantial new expression data. Our analyses show that Anolis sex chromosomes represent an ancient XY system that originated at least ≈160 million years ago in the ancestor of Iguania lizards, shortly after the separation from the snake lineage. The age of this system approximately coincides with the ages of the avian and two mammalian sex chromosomes systems. To compensate for the almost complete Y Chromosome degeneration, X-linked genes have become twofold up-regulated, restoring ancestral expression levels. The highly efficient dosage compensation mechanism of Anolis represents the only vertebrate case identified so far to fully support Ohno’s original dosage compensation hypothesis. Further analyses reveal that X up-regulation occurs only in males and is mediated by a male-specific chromatin machinery that leads to global hyperacetylation of histone H4 at lysine 16 specifically on the X Chromosome. The green anole dosage compensation mechanism is highly reminiscent of that of the fruit fly, Drosophila melanogaster Altogether, our work unveils the convergent emergence of a Drosophila-like dosage compensation mechanism in an ancient reptilian sex chromosome system and highlights that the evolutionary pressures imposed by sex chromosome dosage reductions in different amniotes were resolved in fundamentally different ways.

PMID: 29133310

 

 

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Nucleic Acids Res.: auth.: group Stasiak

Nucleic Acids Res. 2017 Nov 13. doi: 10.1093/nar/gkx1123. [Epub ahead of print]

Transcription-induced supercoiling as the driving force of chromatin loop extrusion during formation of TADs in interphase chromosomes.

Racko D1,2,3Benedetti F1,4Dorier J1,4Stasiak A1,2.

Abstract

Using molecular dynamics simulations, we show here that growing plectonemes resulting from transcription-induced supercoiling have the ability to actively push cohesin rings along chromatin fibres. The pushing direction is such that within each topologically associating domain (TAD) cohesin rings forming handcuffs move from the source of supercoiling, constituted by RNA polymerase with associated DNA topoisomerase TOP1, towards borders of TADs, where supercoiling is released by topoisomerase TOPIIB. Cohesin handcuffs are pushed by continuous flux of supercoiling that is generated by transcription and is then progressively released by action of TOPIIB located at TADs borders. Our model explains what can be the driving force of chromatin loop extrusion and how it can be ensured that loops grow quickly and in a good direction. In addition, the supercoiling-driven loop extrusion mechanism is consistent with earlier explanations proposing why TADs flanked by convergent CTCF binding sites form more stable chromatin loops than TADs flanked by divergent CTCF binding sites. We discuss the role of supercoiling in stimulating enhancer promoter contacts and propose that transcription of eRNA sends the first wave of supercoiling that can activate mRNA transcription in a given TAD.

PMID: 29140466
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Nucleic Acids Res.: auth.: group Dessimoz

Nucleic Acids Res. 2017 Nov 2. doi: 10.1093/nar/gkx1019. [Epub ahead of print]

The OMA orthology database in 2018: retrieving evolutionary relationships among all domains of life through richer web and programmatic interfaces.

Abstract

The Orthologous Matrix (OMA) is a leading resource to relate genes across many species from all of life. In this update paper, we review the recent algorithmic improvements in the OMA pipeline, describe increases in species coverage (particularly in plants and early-branching eukaryotes) and introduce several new features in the OMA web browser. Notable improvements include: (i) a scalable, interactive viewer for hierarchical orthologous groups; (ii) protein domain annotations and domain-based links between orthologous groups; (iii) functionality to retrieve phylogenetic marker genes for a subset of species of interest; (iv) a new synteny dot plot viewer; and (v) an overhaul of the programmatic access (REST API and semantic web), which will facilitate incorporation of OMA analyses in computational pipelines and integration with other bioinformatic resources. OMA can be freely accessed at https://omabrowser.org.

PMID: 29106550
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Proc Natl Acad Sci U S A.: auth.: group Reymond & co-auth.: group Herr

Proc Natl Acad Sci U S A. 2017 Oct 31;114(44):E9308-E9317. doi: 10.1073/pnas.1713625114. Epub 2017 Oct 12.

WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy.

Kannan M1,2,3,4,5Bayam E1,2,3,4Wagner C1,2,3,4Rinaldi B6Kretz PF1,2,3,4Tilly P1,2,3,4Roos M7McGillewie L8Bär S6Minocha S5Chevalier C1,2,3,4Po C9Sanger Mouse Genetics ProjectChelly J1,2,3,4Mandel JL1,2,3,4Borgatti R10Piton A1,2,3,4Kinnear C8Loos B7Adams DJ11Hérault Y1,2,3,4Collins SC1,2,3,4,12Friant S6Godin JD1,2,3,4Yalcin B13,2,3,4.

Abstract

The family of WD40-repeat (WDR) proteins is one of the largest in eukaryotes, but little is known about their function in brain development. Among 26 WDR genes assessed, we found 7 displaying a major impact in neuronal morphology when inactivated in mice. Remarkably, all seven genes showed corpus callosum defects, including thicker (Atg16l1Coro1cDmxl2, and Herc1), thinner (Kif21b and Wdr89), or absent corpus callosum (Wdr47), revealing a common role for WDR genes in brain connectivity. We focused on the poorly studied WDR47 protein sharing structural homology with LIS1, which causes lissencephaly. In a dosage-dependent manner, mice lacking Wdr47 showed lethality, extensive fiber defects, microcephaly, thinner cortices, and sensory motor gating abnormalities. We showed that WDR47 shares functional characteristics with LIS1 and participates in key microtubule-mediated processes, including neural stem cell proliferation, radial migration, and growth cone dynamics. In absence of WDR47, the exhaustion of late cortical progenitors and the consequent decrease of neurogenesis together with the impaired survival of late-born neurons are likely yielding to the worsening of the microcephaly phenotype postnatally. Interestingly, the WDR47-specific C-terminal to LisH (CTLH) domain was associated with functions in autophagy described in mammals. Silencing WDR47 in hypothalamic GT1-7 neuronal cells and yeast models independently recapitulated these findings, showing conserved mechanisms. Finally, our data identified superior cervical ganglion-10 (SCG10) as an interacting partner of WDR47. Taken together, these results provide a starting point for studying the implications of WDR proteins in neuronal regulation of microtubules and autophagy.

KEYWORDS:

WD40-repeat proteins; autophagy; corpus callosum agenesis; microcephaly; neurogenesis

PMID: 29078390

 

 

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J Biol Rhythms.: co-auth.: group Gatfield

J Biol Rhythms. 2017 Nov 1:748730417728663. doi: 10.1177/0748730417728663. [Epub ahead of print]

Guidelines for Genome-Scale Analysis of Biological Rhythms.

Abstract

Genome biology approaches have made enormous contributions to our understanding of biological rhythms, particularly in identifying outputs of the clock, including RNAs, proteins, and metabolites, whose abundance oscillates throughout the day. These methods hold significant promise for future discovery, particularly when combined with computational modeling. However, genome-scale experiments are costly and laborious, yielding “big data” that are conceptually and statistically difficult to analyze. There is no obvious consensus regarding design or analysis. Here we discuss the relevant technical considerations to generate reproducible, statistically sound, and broadly useful genome-scale data. Rather than suggest a set of rigid rules, we aim to codify principles by which investigators, reviewers, and readers of the primary literature can evaluate the suitability of different experimental designs for measuring different aspects of biological rhythms. We introduce CircaInSilico, a web-based application for generating synthetic genome biology data to benchmark statistical methods for studying biological rhythms. Finally, we discuss several unmet analytical needs, including applications to clinical medicine, and suggest productive avenues to address them.

KEYWORDS:

ChIP-seq; RNA-seq; biostatistics; circadian rhythms; computational biology; diurnal rhythms; functional genomics; guidelines; metabolomics; proteomics; systems biology

PMID:

 

29098954

 

 

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Nat Methods.: co-auth.: I.Xenarios

Nat Methods. 2017 Oct 31;14(11):1021-1022. doi: 10.1038/nmeth.4471.

SourceData: a semantic platform for curating and searching figures.

PMID: 29088127