Cell type-specificity elements of the immunoglobulin heavy chain gene enhancer.

Abstract

Communicated by W.Schaffner enhancer motifs analyzed are involved in positive rather than negative control of transcription.

A developmental-specific factor binds to suppressor sites flanking the immunoglobulin heavy-chain enhancer.

“…In contrast, the O site is only important for tissue-specific enhancer function as mutations in O af fect enhancer function in B cells but not in fibroblasts (Lenardo et al 1987). In fact when the O site, in con junction with (xE4, is repeated tandemly, it can function as a tissue-specific enhancer (Gerster et al 1987). Fi nally, the sequences flanking the core enhancer are im portant for enhancer repression in inappropriate cells; deletion of these sequences allows the enhancer to func tion in fibroblasts (Imler et al 1987) or kidney cells (Kadesch et al 1986), or in T cells and macrophages as re ported here, even with a wild-type O site.…”

“…Factors that bind to the (xEl,|xE2,and |JLE3 are present in all cell types (Sen and Baltimore 1986a;Weinberger et al 1986;Lenardo et al 1987). In the case of the O site, at least two apparently distinct factors bind to the octamer (Landolfi et al 1986;Staudt et al 1986;Gerster et al 1987;Lenardo et al 1987), one of which is present only in lymphoid cells. On the basis of the discussion of the cis-acting require ments, this implies that this lymphoid-specific factor is important for positive enhancer function.…”

“…Several groups have reported the binding of factors to the heavy-chain enhancer in vitro. At least five different factors that bind to the 'core' enhancer (the PstI-£coRI fragment) have been identified (Augereau and Chambon 1986;Schlokat et al 1986;Sen and Balti more 1986a;Singh et al 1986;Peterson et al 1986;Weinberger et al 1986;Gerster et al 1987). Factor binding also has been observed to regions that flank the enhancer core (Peterson et al 1986).…”

Enhancer sequences and the regulation of gene transcription

“…In our laboratory we have shown the importance of two neighboring sequence motifs, namely the footprint motif number 4 (F4) and the octamer element, both of which are located within a 51-bp DdeI-Hinfl segment of the IgH enhancer [131]. .…”

Identification of a novel factor that interacts with an immunoglobulin heavy-chain promoter and stimulates transcription in conjunction with the lymphoid cell-specific factor OTF2.

“…This transcription factor interacts with the conserved octanucleotide 5'-ATGCAAAT-3', which is present in all known VH promoters and in the inverted orientation in the heavy-chain enhancer and all light-chain variable region gene promoters. In vivo and in vitro studies have shown that this element is the minimal requirement for efficient cell-type-specific transcription (4,8,11,13,15,18,25,29,34,48).Interestingly, a ubiquitous transcription factor, OTF1, mediates the transcription of the ubiquitously expressed histone H2B gene (43) and interacts with octanucleotide elements in small nuclear RNA gene promoters and the simian virus 40 enhancer (5). Both OTF1 (12) and OTF2 (39) have been purified, and the sequence of cloned OTF2 has * Corresponding author.…”