Regulation of chromatin structure plays a central role in transcriptional control and also impacts mRNA post- transcriptional events.The small well-annotated genome, powerful RNAi technology, and rich resource of chromatin mutants of C. elegans make it an excellent system for studies of chromatin function. To provide a framework for such work, we generated a genome-wide map of 18 histone modifications in C. elegans. We found that many modifications are organised into broad chromosomal domains that differentially mark the more recombinagenic distal arm regions and the central regions. In addition, we found that exon and intron sequences are differentially marked by trimethylation of histone H3 K36, a pattern we also found in mouse and human. We are studying the formation and function of the broad domains, and the function of H3K36me3 exon marking and its relationship with splicing.We are also investigating the functions of C. elegans counterparts of major chromatin regulatory complexes that are implicated in human disease including the histone deacetylase complex NuRD, the retinoblastoma complex DRM, and a TIP60 histone acetyltransferase complex.We study the function of these proteins in transcriptional control and development using chromatin immunoprecipitation followed by deep sequencing, global mRNA expression analyses and other genetic and genomic methods.

Cell polarity is important for many of the functions of animal cells, such as migration, axis formation, and asymmetric cell division. Many of the known molecules involved in cell polarity are conserved across animals, however, the mechanisms by which these function are not well understood. We use the one-celled C. elegans embryo to investigate the polarity cue, its reception, and how polarisation leads to downstream events such as asymmetric spindle positioning.We have completed a large number of genetic interaction RNAi screens that have identified many new cell polarity genes. We are incorporating these into a large cell polarity network and probing their functions using a range of techniques, including live cell imaging, genetics, and biochemistry.

Histone modifications are found in broad chromosomal domains in C.elegans.

Chromatin immunoprecipitation followed by high-throughput sequencing reveals common sites occupied by different chormatin regulatory complexes.

Plain English:
We study two aspects of biology. The first is cell polarity. Nearly all cells have polarity, which means that they are different on one side than the other: the skin has an obvious inside and outside, and these differences are necessary for cells to make a tight seal. Loss of cell polarity contributes to tumour formation. We study how cells become polarised and how they use this information. Because the ways that cells acquire polarity are very similar in all animals, we can make rapid progress by studying an organism where experiments are easy to conduct: the nematode worm C. elegans. Our results help the understanding of cell polarity in humans. Second, we study how genes (regions of DNA) are turned on or off. In order for cells to carry out their functions, it is necessary that the correct set of genes is active: for example, different genes are on in muscle cells compared to nerve cells. In cancer cells, these on and off "programs" are disrupted. We study how proteins that bind to DNA change the activity of genes. Again, because these proteins are similar in all animals, our studies in C. elegans are relevant to humans.

Selected publications:

• Liu T, Ahringer J et al (2011) Broad chromosomal domains of histone modification patterns in C. elegans Genome Research 21, 227-236.

• Gerstein MB, Ahringer J et al (2010) Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project. Science 330, 1775-1787

• Egelhofer TA, Ahringer J et al (2010) Assessment of histone-modification antibody quality Nature Structural and Molecular Biology 18, 91-93

• Kolasinska-Zwierz P, Down T, Latorre I, Liu T, Liu XS and Ahringer J (2009) Differential chromatin marking of introns and expressed exons by H3K36me3 Nature Genetics 41, 376-381

• St Johnston D and Ahringer J (2010) Cell polarity in eggs and epithelia: parallels and diversity Cell 141, 757- 774

synMuv proteins encode hornologs of chromatin regulators found in complexes that modify histones or move nucleosomes.

Interconnected cell polarity network derived from genetic interaction RNAi screening.