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25.10.16 Ahringer lab study of chromatin domains finds separation of genes with different functions

last modified Oct 26, 2016 02:11 PM
This PNAS paper shows that the higher-order structure of chromatin exhibits domains separating broadly-expressed genes from those that are developmentally regulated
25.10.16 Ahringer lab study of chromatin domains finds separation of genes with different functions

From Fig. 6: Model for regulation of chromatin domains

Stable Caenorhabditis elegans chromatin domains separate broadly expressed and developmentally regulated genes

Kenneth J. Evans, Ni Huang, Przemyslaw Stempor, Michael A. Chesney, Thomas A. Down & Julie Ahringer (2016) PNAS [Published online before print; October 25, 2016] DOI: 10.1073/pnas.1608162113

 

The Ahringer group applied chromatin state mapping to two developmental stages of the model organism C. elegans and use the resulting maps to investigate genome domain organization and its regulation.

'Significance statement' from the paper

Genomes are organized into domains of different structure and activity, yet our understanding of their formation and regulation is poor. We show that Caenorhabditis elegans chromatin domain organization in early embryos and third-larval stage animals is remarkably similar despite the two developmental stages containing very different cell types. Chromatin domains separate genes into those with stable versus developmentally regulated expression. Analyses of chromatin domain structure suggest that transcription regulation and germ-line chromatin regulation play roles in separating chromatin domains. Our results further our understanding of genome domain organization.

Abstract from the paper

Eukaryotic genomes are organized into domains of differing structure and activity. There is evidence that the domain organization of the genome regulates its activity, yet our understanding of domain properties and the factors that influence their formation is poor. Here, we use chromatin state analyses in early embryos and third-larval stage (L3) animals to investigate genome domain organization and its regulation in Caenorhabditis elegans. At both stages we find that the genome is organized into extended chromatin domains of high or low gene activity defined by different subsets of states, and enriched for H3K36me3 or H3K27me3, respectively. The border regions between domains contain large intergenic regions and a high density of transcription factor binding, suggesting a role for transcription regulation in separating chromatin domains. Despite the differences in cell types, overall domain organization is remarkably similar in early embryos and L3 larvae, with conservation of 85% of domain border positions. Most genes in high-activity domains are expressed in the germ line and broadly across cell types, whereas low-activity domains are enriched for genes that are developmentally regulated. We find that domains are regulated by the germ-line H3K36 methyltransferase MES-4 and that border regions show striking remodeling of H3K27me1, supporting roles for H3K36 and H3K27 methylation in regulating domain structure. Our analyses of C. elegans chromatin domain structure show that genes are organized by type into domains that have differing modes of regulation.

 

 Reproduced from the paper under CC-BY 4.0 international licence. 

 

Read more about research in the Ahringer lab.

Watch Julie Ahringer describe her research topics on video.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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