02022nas a2200181   4500008004100000022001400041245008800055210006900143260000800212300000800220490000700228520140000235100001901635700002401654700002401678700002301702856011501725       2018                        eng d  a0305-104800aTHiCweed: fast, sensitive detection of sequence features by clustering big datasets0 aTHiCweed fast sensitive detection of sequence features by cluste  cMAR  ae290 v463 a<p>We present THiCweed, a new approach to analyzing transcription factor binding data from high-throughput chromatin immunoprecipitation-sequencing (ChIP-seq) experiments. THiCweed clusters bound regions based on sequence similarity using a divisive hierarchical clustering approach based on sequence similarity within sliding windows, while exploring both strands. ThiCweed is specially geared toward data containing mixtures of motifs, which present a challenge to traditional motif-finders. Our implementation is significantly faster than standard motif-finding programs, able to process 30 000 peaks in 1-2 h, on a single CPU core of a desktop computer. On synthetic data containing mixtures of motifs it is as accurate or more accurate than all other tested programs. THiCweed performs best with large `window' sizes (&gt;50 bp), much longer than typical binding sites (7-15 bp). On real data it successfully recovers literature motifs, but also uncovers complex sequence characteristics in flanking DNA, variant motifs and secondary motifs even when they occur in &lt;5% of the input, all of which appear biologically relevant. We also find recurring sequence patterns across diverse ChIP-seq datasets, possibly related to chromatin architecture and looping. THiCweed thus goes beyond traditional motif finding to give new insights into genomic transcription factor-binding complexity.</p>1 aAgrawal, Ankit1 aSambare, Snehal, V.1 aNarlikar, Leelavati1 aSiddharthan, Rahul  uhttps://library.ncl.res.in/content/thicweed-fast-sensitive-detection-sequence-features-clustering-big-datasets02543nas a2200253   4500008004100000022001400041245005900055210005900114260000800173300001200181490000700193520177800200100002301978700001802001700002102019700001702040700001902057700002602076700002402102700002602126700002302152700002002175856009402195       2021                        eng d  a1088-905100aOrc4 spatiotemporally stabilizes centromeric chromatin0 aOrc4 spatiotemporally stabilizes centromeric chromatin  cAPR  a607-6210 v313 a<p>The establishment of centromeric chromatin and its propagation by the centromere-specific histone CENPA is mediated by epigenetic mechanisms in most eukaryotes. DNA replication origins, origin binding proteins, and replication timing of centromere DNA are important determinants of centromere function. The epigenetically regulated regional centromeres in the budding yeast Candida albicans have unique DNA sequences that replicate earliest in every chromosome and are clustered throughout the cell cycle. In this study, the genome-wide occupancy of the replication initiation protein Orc4 reveals its abundance at all centromeres in C. albicans. Orc4 is associated with four different DNA sequence motifs, one of which coincides with tRNA genes (tDNA) that replicate early and cluster together in space. Hi-C combined with genome-wide replication timing analyses identify that early replicating Orc4-bound regions interact with themselves stronger than with late replicating Orc4-bound regions. We simulate a polymer model of chromosomes of C. albicans and propose that the early replicating and highly enriched Orc4-bound sites preferentially localize around the clustered kinetochores. We also observe that Orc4 is constitutively localized to centromeres, and both Orc4 and the helicase Mcm2 are essential for cell viability and CENPA stability in C. albicans. Finally, we show that new molecules of CENPA are recruited to centromeres during late anaphase/telophase, which coincides with the stage at which the CENPA-specific chaperone Scm3 localizes to the kinetochore. We propose that the spatiotemporal localization of Orc4 within the nucleus, in collaboration with Mcm2 and Scm3, maintains centromeric chromatin stability and CENPA recruitment in C. albicans.</p>1 aSreekumar, Lakshmi1 aKumari, Kiran1 aGuin, Krishnendu1 aBakshi, Asif1 aVarshney, Neha1 aThimmappa, Bhagya, C.1 aNarlikar, Leelavati1 aPadinhateeri, Ranjith1 aSiddharthan, Rahul1 aSanyal, Kaustuv  uhttps://library.ncl.res.in/content/orc4-spatiotemporally-stabilizes-centromeric-chromatin