HMGA1 co-activates transcription in B cells through indirect association with DNA.

TitleHMGA1 co-activates transcription in B cells through indirect association with DNA.
Publication TypeJournal Article
Year of Publication2003
JournalThe Journal of biological chemistry
Volume278
Issue43
Pagination42106-14
Date Published2003 Oct 24
ISSN0021-9258
AbstractThe immunoglobulin heavy chain enhancer, or mu enhancer, is required for B cell development. Only the appropriate combination of transcription factors results in B cell-specific enhancer activation. HMGA1 (formerly (HMG-I(Y)) is a proposed co-activator of the ETS transcription factors required for mu enhancer activity. HMGA1 associates with the ETS factor PU.1, resulting in changes in PU.1 structure, and enhanced transcriptional synergy with Ets-1 on the mu enhancer in nonlymphoid cells. New data show HMGA1 directly interacts with Ets-1 in addition to PU.1. In vitro HMGA1/Ets-1 interaction facilitates Ets-1/mu enhancer binding in the absence of an HMGA1.Ets-1.DNA complex. To address whether HMGA1 is present in the transcriptionally active mu nucleoprotein complex, we completed DNA pull-down assays to detect protein tethering in the context of protein/DNA interaction. Results show that HMGA1 is not tightly associated with mu enhancer DNA through PU.1 or Ets-1, despite strong associations between these proteins in solution. However, chromatin immunoprecipitation assays show HMGA1 associates with the endogenous enhancer in B cells. Furthermore, antisense HMGA1 substantially decreases mu enhancer activity in B cells. Taken together, these data suggest that HMGA1 functions as a transcriptional mu enhancer co-activator in B cells through indirect association with DNA.
URLhttp://www.jbc.org/cgi/pmidlookup?view=long&pmid=12907668
DOI10.1074/jbc.M308586200
PubMed Linkhttp://www.ncbi.nlm.nih.gov/pubmed/12907668?dopt=Abstract
Short TitleJ Biol Chem