Determinants of Chromosome Architecture: Insulator Pairing in cis and in trans.

TitleDeterminants of Chromosome Architecture: Insulator Pairing in cis and in trans.
Publication TypeJournal Article
Year of Publication2016
AuthorsFujioka, M, Mistry, H, Schedl, P, Jaynes, JB
JournalPLoS Genet
Volume12
Issue2
Paginatione1005889
Date Published2016 Feb
ISSN1553-7404
KeywordsAnimals, Animals, Genetically Modified, Chromosomes, Insect, Drosophila melanogaster, Drosophila Proteins, Embryo, Nonmammalian, Genes, Reporter, Green Fluorescent Proteins, Homeodomain Proteins, Insulator Elements, Lac Operon, Transcription Factors
Abstract

<p>The chromosomes of multicellular animals are organized into a series of topologically independent looped domains. This domain organization is critical for the proper utilization and propagation of the genetic information encoded by the chromosome. A special set of architectural elements, called boundaries or insulators, are responsible both for subdividing the chromatin into discrete domains and for determining the topological organization of these domains. Central to the architectural functions of insulators are homologous and heterologous insulator:insulator pairing interactions. The former (pairing between copies of the same insulator) dictates the process of homolog alignment and pairing in trans, while the latter (pairing between different insulators) defines the topology of looped domains in cis. To elucidate the principles governing these architectural functions, we use two insulators, Homie and Nhomie, that flank the Drosophila even skipped locus. We show that homologous insulator interactions in trans, between Homie on one homolog and Homie on the other, or between Nhomie on one homolog and Nhomie on the other, mediate transvection. Critically, these homologous insulator:insulator interactions are orientation-dependent. Consistent with a role in the alignment and pairing of homologs, self-pairing in trans is head-to-head. Head-to-head self-interactions in cis have been reported for other fly insulators, suggesting that this is a general principle of self-pairing. Homie and Nhomie not only pair with themselves, but with each other. Heterologous Homie-Nhomie interactions occur in cis, and we show that they serve to delimit a looped chromosomal domain that contains the even skipped transcription unit and its associated enhancers. The topology of this loop is defined by the heterologous pairing properties of Homie and Nhomie. Instead of being head-to-head, which would generate a circular loop, Homie-Nhomie pairing is head-to-tail. Head-to-tail pairing in cis generates a stem-loop, a configuration much like that observed in classical lampbrush chromosomes. These pairing principles provide a mechanistic underpinning for the observed topologies within and between chromosomes. </p>

DOI10.1371/journal.pgen.1005889
Alternate JournalPLoS Genet.
PubMed ID26910731
PubMed Central IDPMC4765946
Grant ListR01GM050231 / GM / NIGMS NIH HHS / United States
R01 GM050231 / GM / NIGMS NIH HHS / United States
R01 GM043432 / GM / NIGMS NIH HHS / United States
R01GM043432 / GM / NIGMS NIH HHS / United States
P30 CA056036 / CA / NCI NIH HHS / United States