KIP publications

Thymic central tolerance comprehensively imprints the T-cell receptor
repertoire before T cells seed the periphery. Medullary
thymic epithelial cells (mTECs) play a pivotal role in this process by
virtue of promiscuous expression of tissue-restricted autoantigens.
The molecular regulation of this unusual gene expression, in
particular the involvement of epigenetic mechanisms is only poorly
understood. By studying promiscuous expression of the mouse
casein locus, we report that transcription of this locus proceeds
from a delimited region (“entry site”) to increasingly complex patterns
along with mTEC maturation. Transcription of this region is
preceded by promoter demethylation in immature mTECs followed
upon mTEC maturation by acquisition of active histone marks and
local locus decontraction. Moreover, analysis of two additional
gene loci showed that promiscuous expression is transient in single
mTECs. Transient gene expression could conceivably add to the
local diversity of self-antigen display thus enhancing the efficacy
of central tolerance.