Constitutive nuclear factor (NF)-kappaB activation in haematological 
malignancies is caused in several cases by loss of function mutations within the 
coding sequence of NF-kappaB inhibitory molecules such as IkappaBalpha or p100. 
Hut-78, a truncated form of p100, constitutively generates p52 and contributes 
to the development of T-cell lymphomas but the molecular mechanism underlying 
this oncogenic potential remains unclear. We show here that MMP9 gene expression 
is induced through the alternative NF-kappaB-activating pathway in fibroblasts 
and also on Hut-78 or p52 overexpression in fibroblasts as well as in lymphoma 
cells. p52 is critical for Hut-78-mediated MMP9 gene induction as a Hut-78 
mutant as well as other truncated NF-kappaB2 proteins that are not processed 
into p52 failed to induce the expression of this metalloproteinase. Conversely, 
MMP9 gene expression is impaired in p52-depleted HUT-78 cells. Interestingly, 
MLL1 and MLL2 H3K4 methyltransferase complexes are tethered by p52 on the MMP9 
but not on the IkappaBalpha promoter, and the H3K4 trimethyltransferase activity 
recruited on the MMP9 promoter is impaired in p52-depleted HUT-78 cells. 
Moreover, MLL1 and MLL2 are associated with Hut-78 in a native 
chromatin-enriched extract. Thus, we identified a molecular mechanism by which 
the recruitment of a H3K4 histone methyltransferase complex on the promoter of a 
NF-kappaB-dependent gene induces its expression and potentially the invasive 
potential of lymphoma cells harbouring constitutive activity of the alternative 
NF-kappaB-activating pathway.