Person: Viswanadham, Vinay
Loading...
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
Viswanadham
First Name
Vinay
Name
Viswanadham, Vinay
1 results
Search Results
Now showing 1 - 1 of 1
Publication Uncovering Epigenetic Control Elements in B-Cell Subset Development(2016-05-24) Viswanadham, Vinay; Pillai, Shiv S.; Mahajan, Vinay S.During development, B-cells transition through several different cell states, each of which has distinct characteristics and roles in the immune system at large. A major challenge in B-cell biology is to elucidating the mechanisms that regulate proper transitions between sequences of cell state. Such pathways are necessary to understand the core biology behind B-cells as well as potential points of failure in B-cell disorders. One persisting question is on the nature of the regulatory mechanisms that control the decision of a developing B-cell to become one of three different cell fates for developing B-cells: the B-1a cells, the marginal zone B-cells, and the follicular B-cells. Although the role of transcription factors in controlling gene expression relevant this fate decision has been the subject of intense scientific interest, the overarching mechanisms involving structural changes to chromatin that permit transcription factor binding are less well explored. In particular, the role of chromatin accessibility in regulating such fate decisions remains an unexplored aspect of B-cell developmental regulation. Using ATAC-seq to detect accessible chromatin and RNA-seq to characterize gene expression differences in mouse B-1a, immature, marginal zone, and follicular B-cells; we characterized the landscape of open chromatin in the four subsets. We identify subset-specific sets of accessible chromatin enriched in distinct sets transcription factor binding sequences. Upon exploring the associations between the accessible chromatin landscape and the transcriptomes of the marginal zone and follicular B-cells, we find that the most differentially expressed genes in each of the two subsets are the genes with the top 1% of associations to accessible chromatin of all genes and that this set is enriched for known B-cell genes and potentially novel regulators. Furthermore, we cluster stretches of accessible chromatin into enhancers and identify a subset strongly enriched in accessibility signal, suggesting that super-enhancer elements exist in this landscape. Overall, we have implemented a method to explore the epigenetic control of gene expression in B-cell subsets and to explore how chromatin accessibility can underlie important features of the process by which a B-cell becomes part of a unique subset.