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Functional Genomics​ (LFG)

MPRA


Team leader:  Christine Plançon
E-mail: christine.plancon[at]cnrgh.fr​

Team leader: Masazumi Takahashi
E-mail: masazumi.takahashi[at]cnrgh.fr

Published on 13 May 2022



Functional analysis of immunoglobulin heavy chain gene enhancer using massively parallel reporter assay (MPRA)

Functional study of the gene is a work to try millions of keys to open a door. We still have only limited knowledge to understand the gene function from the primary structural read after decades of the human genome sequence. Development of sequence technology is offering us many new tools. Among them, RNAseq enables a reproducible and accurate measurement of gene expression by counting the number of sequences. On the other hand, oligo nucleotide synthesis has also a progress to generate long and various many desired sequences at once. The massively parallel reporter assay (MPRA) applies these technologies to about hundreds base pair sequence elements. 

The enhancer of the immunoglobulin (Ig or BCR, B-cell receptor) gene is one of the best studied mammalian gene enhancer, which has a key role in B cell immune system. We have been working on functional study of Ig heavy chain (IgH) intron enhancer (Eµ) by introducing various mutations in EBV transformed B cell lines. MPRA makes us to know the relationship between every mutation and gene expression.

Specifically, we are interested in the role of Eµ at B-cell allelic exclusion. For production of right kind of antibodies, allelic exclusion is a necessary mechanism. It is predicted that the disturbance of the mechanism can cause autoimmune disease. Currently, vaccination to COVID-19 is reported to cause, although it is rare, an autoimmune reaction. Protection from the adverse effect, it is important to know if there exist susceptible genotypes.