PgmNr W4111: A developmental map of accessible chromatin in C. elegans.

Authors:
Yan DONG; Jürgen Jänes; Alex Appert; Djem Kissiov; Julie Ahringer


Institutes
The Gurdon Institute, University of Cambridge, Cambridge, UK.


Keyword: Chromatin organization

Abstract:

Genome-wide mapping of regulatory regions is important for understanding developmental gene regulation. Regulatory elements such as promoters and enhancers are often nucleosome-depleted, rendering them accessible to digestion by a low concentration of DNase I. Regions of open chromatin are also susceptible to transposition of sequencing adaptors by the transposase Tn5 (ATAC-seq). Nucleosome occupancy or positioning can be mapped by digestion using MNase. In C. elegans, chromatin accessibility data is currently limited to a single stage generated using DNase-chip whereas MNase maps are only available for two developmental stages.

We have used ATAC-seq, DNAse-seq, and MNase-seq to map genome-wide accessibility at six developmental stages: embryos, four larval stages and young adults. Using ATAC-seq, we define more than 30,000 accessible sites across development, which show agreement with developmental TF ChIP binding patterns from the modENCODE project. Most accessible sites are present at multiple stages, with stage specific sites primarily occurring in embryos and young adults.

Although many accessible sites are detectable at multiple stages, the majority of sites change in accessibility across development.  We observe two common patterns of developmental changes — regions that decrease over development and regions that increase over development. Regions with increasing accessibility are characterised by lower G+C content compared to regions with decreasing accessibility. We further characterise regions of open chromatin based on relative accessibility to DNase I, nucleosome occupancy, transcription factor or chromatin remodeller binding, and histone modifications.