1: Nat Immunol. 2004 Oct;5(10):1069-77. Epub 2004 Sep 12. 

Early B cell factor cooperates with Runx1 and mediates epigenetic changes
associated with mb-1 transcription.

Maier H, Ostraat R, Gao H, Fields S, Shinton SA, Medina KL, Ikawa T, Murre C,
Singh H, Hardy RR, Hagman J.

Integrated Department of Immunology, National Jewish Medical and Research
Center, Denver, Colorado 80206, USA.

Cd79a (called mb-1 here) encodes the Ig-alpha signaling component of the B cell
receptor. The early B cell-specific mb-1 promoter was hypermethylated at CpG
dinucleotides in hematopoietic stem cells but became progressively unmethylated
as B cell development proceeded. The transcription factor Pax5 activated
endogenous mb-1 transcription in a plasmacytoma cell line, but could not when
the promoter was methylated. In this context, early B cell factor (EBF), a
transcription factor required for B lymphopoiesis, potentiated activation of
mb-1 by Pax5. EBF and the basic helix-loop-helix transcription factor E47 each
contributed to epigenetic modifications of the mb-1 promoter, including CpG
demethylation and nucleosomal remodeling. EBF function was enhanced by
interaction with the transcription factor Runx1. These data suggest a molecular
basis for the hierarchical dependence of Pax5 function on EBF and E2A in B
lymphocyte development.

PMID: 15361869 [PubMed - indexed for MEDLINE]


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2: J Biol Chem. 1999 Aug 27;274(35):24671-6. 

AML1 (CBFalpha2) cooperates with B cell-specific activating protein (BSAP/PAX5)
in activation of the B cell-specific BLK gene promoter.

Libermann TA, Pan Z, Akbarali Y, Hetherington CJ, Boltax J, Yergeau DA, Zhang
DE.

New England Baptist Bone and Joint Institute, Beth Israel Deaconess Medical
Center, Harvard Medical School, Boston, Massachusetts 02115, USA.

AML1 plays a critical role during hematopoiesis and chromosomal translocations
involving AML1 are commonly associated with different forms of leukemia,
including pre-B acute lymphoblastic leukemia. To understand the function of AML1
during B cell differentiation, we analyzed regulatory regions of B cell-specific
genes for potential AML1-binding sites and have identified a putative
AML1-binding site in the promoter of the B cell-specific tyrosine kinase gene,
blk. Gel mobility shift assays and transient transfection assays demonstrate
that AML1 binds specifically to this site in the blk promoter and this binding
site is important for blk promoter activity. Furthermore, in vitro binding
analysis revealed that the AML1 runt DNA-binding domain physically interacts
with the paired DNA-binding domain of BSAP, a B cell-specific transcription
factor. BSAP has been shown previously to be important for B cell-specific
regulation of the blk gene. Physical interaction of AML1 with BSAP correlates
with functional cooperativity in transfection studies where AML1 and BSAP
synergistically activate blk promoter transcription by more than 50-fold. These
results demonstrate physical and functional interactions between AML1 and BSAP
and suggest that AML1 is an important factor for regulating a critical B
cell-specific gene, blk.

PMID: 10455134 [PubMed - indexed for MEDLINE]


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