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Articles by F Chiaromonte
Total Records ( 3 ) for F Chiaromonte
  E. M Kvikstad , F Chiaromonte and K. D. Makova

Recent studies have revealed that insertions and deletions (indels) are more different in their formation than previously assumed. What remains enigmatic is how the local DNA sequence context contributes to these differences. To investigate the relative impact of various molecular mechanisms to indel formation, we analyzed sequence contexts of indels in the non protein- or RNA-coding, nonrepetitive (NCNR) portion of the human genome. We considered small (≤30-bp) indels occurring in the human lineage since its divergence from chimpanzee and used wavelet techniques to study, simultaneously for multiple scales, the spatial patterns of short sequence motifs associated with indel mutagenesis. In particular, we focused on motifs associated with DNA polymerase activity, topoisomerase cleavage, double-strand breaks (DSBs), and their repair. We came to the following conclusions. First, many motifs are characterized by unique enrichment profiles in the vicinity of indels vs. indel-free portions of the genome, verifying the importance of sequence context in indel mutagenesis. Second, only limited similarity in motif frequency profiles is evident flanking insertions vs. deletions, confirming differences in their mutagenesis. Third, substantial similarity in frequency profiles exists between pairs of individual motifs flanking insertions (and separately deletions), suggesting "cooperation" among motifs, and thus molecular mechanisms, during indel formation. Fourth, the wavelet analyses demonstrate that all these patterns are highly dependent on scale (the size of an interval considered). Finally, our results depict a model of indel mutagenesis comprising both replication and recombination (via repair of paused replication forks and site-specific recombination).

  S Kosakovsky Pond , S Wadhawan , F Chiaromonte , G Ananda , W. Y Chung , J Taylor , A Nekrutenko and The Galaxy Team

How many species inhabit our immediate surroundings? A straightforward collection technique suitable for answering this question is known to anyone who has ever driven a car at highway speeds. The windshield of a moving vehicle is subjected to numerous insect strikes and can be used as a collection device for representative sampling. Unfortunately the analysis of biological material collected in that manner, as with most metagenomic studies, proves to be rather demanding due to the large number of required tools and considerable computational infrastructure. In this study, we use organic matter collected by a moving vehicle to design and test a comprehensive pipeline for phylogenetic profiling of metagenomic samples that includes all steps from processing and quality control of data generated by next-generation sequencing technologies to statistical analyses and data visualization. To the best of our knowledge, this is also the first publication that features a live online supplement providing access to exact analyses and workflows used in the article.

  Y Cheng , W Wu , S Ashok Kumar , D Yu , W Deng , T Tripic , D. C King , K. B Chen , Y Zhang , D Drautz , B Giardine , S. C Schuster , W Miller , F Chiaromonte , G. A Blobel , M. J Weiss and R. C. Hardison

The transcription factor GATA1 regulates an extensive program of gene activation and repression during erythroid development. However, the associated mechanisms, including the contributions of distal versus proximal cis-regulatory modules, co-occupancy with other transcription factors, and the effects of histone modifications, are poorly understood. We studied these problems genome-wide in a Gata1 knockout erythroblast cell line that undergoes GATA1-dependent terminal maturation, identifying 2616 GATA1-responsive genes and 15,360 GATA1-occupied DNA segments after restoration of GATA1. Virtually all occupied DNA segments have high levels of H3K4 monomethylation and low levels of H3K27me3 around the canonical GATA binding motif, regardless of whether the nearby gene is induced or repressed. Induced genes tend to be bound by GATA1 close to the transcription start site (most frequently in the first intron), have multiple GATA1-occupied segments that are also bound by TAL1, and show evolutionary constraint on the GATA1-binding site motif. In contrast, repressed genes are further away from GATA1-occupied segments, and a subset shows reduced TAL1 occupancy and increased H3K27me3 at the transcription start site. Our data expand the repertoire of GATA1 action in erythropoiesis by defining a new cohort of target genes and determining the spatial distribution of cis-regulatory modules throughout the genome. In addition, we begin to establish functional criteria and mechanisms that distinguish GATA1 activation from repression at specific target genes. More broadly, these studies illustrate how a "master regulator" transcription factor coordinates tissue differentiation through a panoply of DNA and protein interactions.

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