Results and analysis of earth tide observations with the borehole tiltmeter in Poltava

Results of harmonic analysis of eight years earth tides observations with the borehole tiltmeter of the Poltava Gravimetric Observatory are presented. Hight-precision parameters of the main tidal waves and Love´s numbers h and k which practically coincide with similar data from  tiltmetric and gravimetric observations in 25 stations of Ukraine are received. The azimuthal inequality of a factor γ in the NS and EW directions isn't revealed. Resonant influence of the liquid core of Earth coincides with calculated theoretically

Distinct DNA-binding surfaces in the ATPase and linker domains of MutLγ determine its substrate specificities and exert separable functions in meiotic recombination and mismatch repair

<div><p>Mlh1-Mlh3 (MutLγ) is a mismatch repair factor with a central role in formation of meiotic crossovers, presumably through resolution of double Holliday junctions. MutLγ has DNA-binding, nuclease, and ATPase activities, but how these relate to one another and to <i>in vivo</i> functions are unclear. Here, we combine biochemical and genetic analyses to characterize <i>Saccharomyces cerevisiae</i> MutLγ. Limited proteolysis and atomic force microscopy showed that purified recombinant MutLγ undergoes ATP-driven conformational changes. <i>In vitro</i>, MutLγ displayed separable DNA-binding activities toward Holliday junctions (HJ) and, surprisingly, single-stranded DNA (ssDNA), which was not predicted from current models. MutLγ bound DNA cooperatively, could bind multiple substrates simultaneously, and formed higher-order complexes. FeBABE hydroxyl radical footprinting indicated that the DNA-binding interfaces of MutLγ for ssDNA and HJ substrates only partially overlap. Most contacts with HJ substrates were located in the linker regions of MutLγ, whereas ssDNA contacts mapped within linker regions as well as the N-terminal ATPase domains. Using yeast genetic assays for mismatch repair and meiotic recombination, we found that mutations within different DNA-binding surfaces exert separable effects <i>in vivo</i>. For example, mutations within the Mlh1 linker conferred little or no meiotic phenotype but led to mismatch repair deficiency. Interestingly, mutations in the N-terminal domain of Mlh1 caused a stronger meiotic defect than <i>mlh1Δ</i>, suggesting that the mutant proteins retain an activity that interferes with alternative recombination pathways. Furthermore, <i>mlh3Δ</i> caused more chromosome missegregation than <i>mlh1Δ</i>, whereas <i>mlh1Δ</i> but not <i>mlh3Δ</i> partially alleviated meiotic defects of <i>msh5Δ</i> mutants. These findings illustrate functional differences between Mlh1 and Mlh3 during meiosis and suggest that their absence impinges on chromosome segregation not only via reduced formation of crossovers. Taken together, our results offer insights into the structure-function relationships of the MutLγ complex and reveal unanticipated genetic relationships between components of the meiotic recombination machinery.</p></div

Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation

A hallmark of chromosome organization is the partition into transcriptionally active A and repressed B compartments, and into topologically associating domains (TADs). Both structures were regarded to be absent from the inactive mouse X chromosome, but to be re-established with transcriptional reactivation and chromatin opening during X-reactivation. Here, we combine a tailor-made mouse iPSC reprogramming system and high-resolution Hi-C to produce a time course combining gene reactivation, chromatin opening and chromosome topology during X-reactivation. Contrary to previous observations, we observe A/B-like compartments on the inactive X harbouring multiple subcompartments. While partial X-reactivation initiates within a compartment rich in X-inactivation escapees, it then occurs rapidly along the chromosome, concomitant with downregulation of Xist. Importantly, we find that TAD formation precedes transcription and initiates from Xist-poor compartments. Here, we show that TAD formation and transcriptional reactivation are causally independent during X-reactivation while establishing Xist as a common denominator.This work was supported by the European Research Council under the 7th Framework Programme FP7/2007-2013 (ERC Synergy Grant 4D-Genome, grant agreement 609989 to G.J.F.), by the Spanish Ministry of Science, Innovation and Universities (BFU2014-55275-P, BFU2017-88407-P to B.P. and PGC2018-099807-B-I00 to G.J.F.), the Agencia Estatal de Investigación (AEI) (EUR2019-103817 to B.P.), the AXA Research Fund (to B.P.) and the Agencia de Gestio d’Ajuts Universitaris i de Recerca (AGAUR, 2017 SGR 346 to B.P.) and by the NIH grant R35GM124926 to S.F.P. We would like to thank the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership and to the “Centro de Excelencia Severo Ochoa”. We also acknowledge support of the CERCA Programme of the Generalitat de Catalunya. M.B. was supported by a La Caixa International PhD Fellowship