The Regulatory T Cell Lineage Factor Foxp3 Regulates Gene Expression through Several Distinct Mechanisms Mostly Independent of Direct DNA Binding.

Abstract:

:The lineage factor Foxp3 is essential for the development and maintenance of regulatory T cells, but little is known about the mechanisms involved. Here, we demonstrate that an N-terminal proline-rich interaction region is crucial for Foxp3's function. Subdomains within this key region link Foxp3 to several independent mechanisms of transcriptional regulation. Our study suggests that Foxp3, even in the absence of its DNA-binding forkhead domain, acts as a bridge between DNA-binding interaction partners and proteins with effector function permitting it to regulate a large number of genes. We show that, in one such mechanism, Foxp3 recruits class I histone deacetylases to the promoters of target genes, counteracting activation-induced histone acetylation and thereby suppressing their expression.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Xie X,Stubbington MJ,Nissen JK,Andersen KG,Hebenstreit D,Teichmann SA,Betz AG

doi

10.1371/journal.pgen.1005251

subject

Has Abstract

pub_date

2015-06-24 00:00:00

pages

e1005251

issue

6

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-15-00358

journal_volume

11

pub_type

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