Ruth Tabancay interviewed by Maia Mislang

In this interview, originally recorded over Zoom, Ruth Tabancay speaks with Watsonville is in the Heart team member Maia Mislang. Ruth is a Bay Area-based textile and fiber artist. Ruth explains how her mother Esther Galicia immigrated to the United States from the Philippines to attend Hartnell College in Salinas. Esther's immigration to the US was sponsored by her aunt, Paula Galicia. Ruth discusses Esther's twenty-five years of experience working at Green Giant cannery in Watsonville. Ruth also explains that her father Benny Tabancay worked in the dry cleaning business rather than in the agricultural fields like many other men. Throughout the interview Ruth reflects on her time growing up within the Filipino American community in Watsonville, as well as how her identity and experiences impact her current art practice. She fondly recalls participating in Filipino folk dance classes, wearing traditional Filipiniana clothing, playing street games with neighborhood kids, and making decorations Fourth of July parade floats with her mother and other members of the Filipino Women's Club of Watsonville

Common fragile sites are characterized by histone hypoacetylation

Common fragile sites (CFSs) represent large, highly unstable regions of the human genome. CFS sequences are sensitive to perturbation of replication; however, the molecular basis for the instability at CFSs is poorly understood. We hypothesized that a unique epigenetic pattern may underlie the unusual sensitivity of CFSs to replication interference. To examine this hypothesis, we analyzed chromatin modification patterns within the six human CFSs with the highest levels of breakage, and their surrounding non-fragile regions (NCFSs). Chromatin at most of the CFSs analyzed has significantly less histone acetylation than that of their surrounding NCFSs. Trichostatin A and/or 5-azadeoxycytidine treatment reduced chromosome breakage at CFSs. Furthermore, chromatin at the most commonly expressed CFS, the FRA3B, is more resistant to micrococcal nuclease than that of the flanking non-fragile sequences. These results demonstrate that histone hypoacetylation is a characteristic epigenetic pattern of CFSs, and chromatin within CFSs might be relatively more compact than that of the NCFSs, indicating a role for chromatin conformation in genomic instability at CFSs. Moreover, lack of histone acetylation at CFSs may contribute to the defective response to replication stress characteristic of CFSs, leading to the genetic instability characteristic of this regions

Diversity of Eukaryotic DNA Replication Origins Revealed by Genome-Wide Analysis of Chromatin Structure

Eukaryotic DNA replication origins differ both in their efficiency and in the characteristic time during S phase when they become active. The biological basis for these differences remains unknown, but they could be a consequence of chromatin structure. The availability of genome-wide maps of nucleosome positions has led to an explosion of information about how nucleosomes are assembled at transcription start sites, but no similar maps exist for DNA replication origins. Here we combine high-resolution genome-wide nucleosome maps with comprehensive annotations of DNA replication origins to identify patterns of nucleosome occupancy at eukaryotic replication origins. On average, replication origins contain a nucleosome depleted region centered next to the ACS element, flanked on both sides by arrays of well-positioned nucleosomes. Our analysis identified DNA sequence properties that correlate with nucleosome occupancy at replication origins genome-wide and that are correlated with the nucleosome-depleted region. Clustering analysis of all annotated replication origins revealed a surprising diversity of nucleosome occupancy patterns. We provide evidence that the origin recognition complex, which binds to the origin, acts as a barrier element to position and phase nucleosomes on both sides of the origin. Finally, analysis of chromatin reconstituted in vitro reveals that origins are inherently nucleosome depleted. Together our data provide a comprehensive, genome-wide view of chromatin structure at replication origins and suggest a model of nucleosome positioning at replication origins in which the underlying sequence occludes nucleosomes to permit binding of the origin recognition complex, which then (likely in concert with nucleosome modifiers and remodelers) positions nucleosomes adjacent to the origin to promote replication origin function

Transcription initiation activity sets replication origin efficiency in mammalian cells

Genomic mapping of DNA replication origins (ORIs) in mammals provides a powerful means for understanding the regulatory complexity of our genome. Here we combine a genome-wide approach to identify preferential sites of DNA replication initiation at 0.4% of the mouse genome with detailed molecular analysis at distinct classes of ORIs according to their location relative to the genes. Our study reveals that 85% of the replication initiation sites in mouse embryonic stem (ES) cells are associated with transcriptional units. Nearly half of the identified ORIs map at promoter regions and, interestingly, ORI density strongly correlates with promoter density, reflecting the coordinated organisation of replication and transcription in the mouse genome. Detailed analysis of ORI activity showed that CpG island promoter-ORIs are the most efficient ORIs in ES cells and both ORI specification and firing efficiency are maintained across cell types. Remarkably, the distribution of replication initiation sites at promoter-ORIs exactly parallels that of transcription start sites (TSS), suggesting a co-evolution of the regulatory regions driving replication and transcription. Moreover, we found that promoter-ORIs are significantly enriched in CAGE tags derived from early embryos relative to all promoters. This association implies that transcription initiation early in development sets the probability of ORI activation, unveiling a new hallmark in ORI efficiency regulation in mammalian cellsWork in María Gómez’s laboratory is supported by grants from the Spanish Ministry of Education and Science (BFU2007-66827) and the Consejería de Sanidad of the Junta de Castilla y León (SAN196/SA12/07). JSM was supported by a grant from the Portuguese Foundation for Science and Technology (SFRH/BD/ 11824/2003

Microtubule active taxanes inhibit polycystic kidney disease progression in cpk mice

Microtubule active taxanes inhibit polycystic kidney disease progression in cpk mice. Homozygous cpk/cpk mice develop polycystic kidney disease and die of uremia between the fourth and fifth weeks of age. Cpk/cpk mice treated weekly with paclitaxel (Taxol) can live to over six months of age. This dramatic moderation of polycystic kidney disease progression has been postulated to be a result of paclitaxel's ability to stabilize microtubules. In this study, the ability of taxanes with differing abilities to promote spontaneous in vitro assembly of tubulin dimers into microtubules were tested for their ability to inhibit the progression of polycystic kidney disease in polycystic cpk/cpk mice. We found that taxanes that are active in promoting microtubule assembly, including paclitaxel, 10-deactyl-taxol and cephalomannine increased the survival of polycystic cpk/cpk mice significantly longer than control animals. In contrast, the microtubule inactive taxane baccatin-III has no effect on the progression of renal failure in cpk/cpk mice. We conclude that the ability to promote microtubule assembly may be necessary for paclitaxel and related taxanes to modulate the progression of polycystic kidney progression in cpk/cpk mice