Computational Pipelines Connecting Data Wells and Fountains to Information Nuggets

Authors

• D Landsman
• I Zhu
• T Deng
• S Zhang
• M Bustin

Abstract

Genome scale sequencing has become a routine method for biologists to study functional genomics and many aspects of chromatin structure and transcription. In collaboration with experimental laboratories, our group utilizes and develops computational methods and pipelines to analyze and interpret large scale data, particularly next generation sequencing data, to translate into biological insights. One of our major projects is a collaboration with Micheal Bustin’s group in the NCI to study the function of High Mobility Group Proteins, HMGN1 and HMGN2. Studies include their genomic localization, how they affect chromatin structure and transcriptome fidelity in different mouse tissues. Comparisons between WT (wild type) and HMGN single and double knock out mice data revealed that HMGN proteins mainly localize to functional genomic regions in large part delineated by DNase I hypersensitive sites (DHS). HMGN1 and HMGN2 modulate nucleosome structures mainly at CpG island promoters and the two proteins synergistically maintain DHS, especially at enhancers, and transcriptome fidelity. Moreover, the functions of HMGN proteins are tissue specific to an extent. 4C-seq experiments revealed that, although HMGN proteins subtly modulates local chromatin structure and accessibility, they have do not have a significant effect on long-range chromatin interactions.

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