Transcriptional units form the elementary constraining building blocks of the bacterial chromosome
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ABSTRACT:
ORGANISM(S): Escherichia coli
PROVIDER: GSE213028 | GEO | 2023/12/01
REPOSITORIES: GEO
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Project description:The organisation of the genome in nuclear space is an important frontier of biology. Chromosome conformation capture methods such as Hi-C and Micro-C produce genome-wide chromatin contact maps that provide rich data containing quantitative and qualitative information about genome architecture. Most conventional approaches to genome-wide chromosome conformation capture data are limited to the analysis of pre-defined features, and may therefore miss important biological information. One constraint is that biologically important features can be masked by high levels of technical noise in the data. Here we introduce Twins, a replicate-based method for deep learning from chromatin conformation contact maps. Using a Siamese network configuration, Twins learns to distinguish technical noise from biological variation and outperforms image similarity metrics across a range of biological systems. Features extracted by Twins from Hi-C maps after perturbation of cohesin and CTCF reflect the distinct biological functions of cohesin and CTCF in the formation of domains and boundaries, respectively. Twins distance metrics are biologically meaningful, as they mirror the density of cohesin and CTCF binding. Taken together, these properties make Twins an powerful tool for the exploration of chromosome conformation capture data, such as Hi-C capture Hi-C, and Micro-C.
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Project description:Chromosomes in all organisms are highly organized and divided into multiple chromosomal interaction domains, or topological domains. Regions of active, high transcription help establish and maintain domain boundaries, but precisely how this occurs remains unclear. Here, using fluorescence microscopy and chromosome conformation capture in conjunction with deep sequencing (Hi-C), we show that in Caulobacter crescentus both transcription rate and transcript length, independent of concurrent translation, drive the formation of domain boundaries. We find that long, highly expressed genes do not form topological boundaries simply through the inhibition of supercoil diffusion. Instead, our results support a model in which long, active regions of transcription drive local decompaction of the chromosome, with these more open regions of the chromosome forming spatial gaps in vivo that diminish contacts between DNA in neighboring domains. These insights into the molecular forces responsible for domain formation in Caulobacter likely generalize to other bacteria and possibly eukaryotes.
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