YY1 binds to the E3ʹ enhancer and inhibits the expression of the immunoglobulin κ gene via epigenetic modifications

Published on Dec 1, 2018in Immunology5.016
· DOI :10.1111/IMM.12990
Xiaorong Zhou4
Estimated H-index: 4
(Nantong University),
Weiwei Xian1
Estimated H-index: 1
(Nantong University)
+ 6 AuthorsXiao-Ying Wang5
Estimated H-index: 5
(Nantong University)
Sources
Abstract
: The rearrangement and expression of immunoglobulin genes are regulated by enhancers and their binding transcriptional factors that activate or suppress the activities of the enhancers. The immunoglobulin κ (Igκ) gene locus has three important enhancers: the intrinsic enhancer (Ei), 3' enhancer (E3'), and distal enhancer (Ed). Ei and E3' are both required for Igκ gene rearrangement during early stages of B-cell development, whereas optimal expression of the rearranged Igκ gene relies on both E3' and Ed. The transcription factor YY1 affects the expression of many genes involved in B-cell development, probably by mediating interactions between their enhancers and promoters. Herein, we found that YY1 binds to the E3' enhancer and suppresses Igκ expression in B lymphoma cells by epigenetically modifying the enhancer. Knocking down YY1 enhanced Igκ expression, which was associated with increased levels of E2A (encoded by the TCF3 gene) and its binding to the E3' enhancer. Moreover, in germinal centre B cells and plasma cells, YY1 expression was reversely associated with Igκ levels, implying that YY1 might facilitate antibody affinity maturation in germinal centre B cells through the transient attenuation of Igκ expression.
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