Year: 1998
Type: article
Abstract: Transcription of the Ig H chain germline transcripts is a prerequisite for class switching. Expression of the epsilon germline transcript is induced by IL-4 and requires the integrity of a composite IL-4 response element. The element is bound by the IL-4-inducible transcription factor Stat6 and one or more members of the CAAT/enhancer-binding protein (C/EBP) family, a constitutively expressed class of transcription factors. Here, we show that Stat6 and C/EBP beta cooperate to synergistically activate transcription from the epsilon element. The effect was most pronounced in lymphoid cells, and the activation domains of both proteins were required to achieve this synergy. Although other members of the C/EBP family are able to bind the element, very little cooperativity was seen with C/EBP alpha and none with C/EBP gamma. In fact, C/EBP gamma was able to inhibit IL-4-induced reporter activity. Stat6 and C/EBP beta bind the IL-4 response element simultaneously. The fast dissociation rate apparent when Stat6 binds this DNA element alone is slowed when C/EBP beta binds at the neighboring site. These data suggest a mechanism whereby C/EBP beta stabilizes Stat6 binding at this element, thereby increasing the likelihood that both of their activation domains will interact, possibly with other factors, to activate transcription in an IL-4-dependent manner.
Source: The Journal of Immunology
Authors: Thomas Mikita, Masae Kurama, Ulrike Schindler
Institution: Surrozen, Inc. (United States)
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funder: McKnight Foundation
OpenAlex ID: W4313333868