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Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming.

ABSTRACT: Chromatin structure determines DNA accessibility. We compare nucleosome occupancy in mouse and human embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs) and differentiated cell types using MNase-seq. To address variability inherent in this technique, we developed a bioinformatic approach to identify regions of difference (RoD) in nucleosome occupancy between pluripotent and somatic cells. Surprisingly, most chromatin remains unchanged; a majority of rearrangements appear to affect a single nucleosome. RoDs are enriched at genes and regulatory elements, including enhancers associated with pluripotency and differentiation. RoDs co-localize with binding sites of key developmental regulators, including the reprogramming factors Klf4, Oct4/Sox2 and c-Myc. Nucleosomal landscapes in ESC enhancers are extensively altered, exhibiting lower nucleosome occupancy in pluripotent cells than in somatic cells. Most changes are reset during reprogramming. We conclude that changes in nucleosome occupancy are a hallmark of cell differentiation and reprogramming and likely identify regulatory regions essential for these processes.

SUBMITTER: West JA

PROVIDER: S-EPMC4217530 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abundance-occupancy (A-O) relationships are widely documented for many organismal groups and regions, and have been used to gain an understanding of regional population and community trends. Monitoring changes in abundance and occupancy over time may be what is required to document changes in conservation status and needs for some species, communities, or areas.We hypothesize that if there is a higher proportion of declining species in one group of species compared with another (e.g., migratory species vs. permanent residents), then a consequence of that difference will be vastly different abundance-occupancy relationships. If this difference persists through time, then the resulting A-O relationships between the groups will continue to diverge.For neotropical migrants, short-distance migrants, and permanent resident birds of North America, we assess the numbers of declining species over 1969-2009. We further test for differences in the A-O relationship across these three groups, and in rates of change in abundance and occupancy separately.We find significant differences in numbers of declining species across the migratory groups, a significant decline in the A-O relationship for permanent residents, a significant increase for Neotropical migrants, and a nonsignificant decline for short-distance migrants over the 40 years. Further, abundances are not changing at different rates but occupancies are consistently greater over time for neotropical migrants versus permanent residents, likely driving the changes in A-O relationships observed.In these analyses, we documented changing A-O trends for different groups of species, over a relatively long time period for ecological studies, one of only a few studies to examine A-O relationships over time. Further, we have shown that a temporally unvarying abundance-occupancy relationship is not universal, and we posit that variability in A-O relationships is due to human impacts on habitats, coupled with variation in species' abilities to respond to human impacts.

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Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming.

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