A protein binding to the Jk recombination sequence of immunoglobulin genes contains a sequence related to the integrase motif

Abstract

Site-specific recombination requires conserved DNA sequences specific to each system, and system-specific proteins that recognize specific DNA sequences. The site-specific recombinases seem to fall into at least two families, based on their protein structure and chemistry of strand breakage. One of these is the resolvase-invertase family, members of which seem to form a serine-phosphate linkage with DNA. Members of the other family, called the integrase family, contain a conserved tyrosine residue that forms a covalent linkage with the 3'-phosphate of DNA at the site of recombination. Structural comparison of integrases shows that these proteins share a highly conserved 40-residue motif. V-(D)-J recombination of the immunoglobulin gene requires conserved recombination signal sequences (RS) of a heptamer CACTGTG and a T-rich nonamer GGTTTTTGT, which are separated by a spacer sequence of either 12 or 23 bases We have recently purified, almost to homogeneity, a protein that specifically binds to the immunoglobulin J kappa RS containing the 23-base-pair spacer sequence. By synthesizing probes on the basis of partial amino-acid sequences of the purified protein, we have now isolated and characterized the complementary DNA of this protein. The amino-acid sequence deduced from the cDNA sequence reveals that the J kappa RS-binding protein has a sequence similar to the 40-residue motif of integrases of phages, bacteria and yeast, indicating that this protein could be involved in V-(D)-J recombination as a recombinase.

Intracellular forms of human NOTCH1 interact at distinctly different levels with RBP-Jkappa in human B and T cells

“…Therefore, signaling by NOTCH1 can be mediated by its association with RBP-J and potential other factors acting at the promoters. [12][13][14][15] Genetic studies have also suggested a functional association with these two molecules in that studies in Drosophila and C. elegans encoding homologs of mammalian NOTCH1 indicate that RBP-J acts downstream of NOTCHI. [16][17][18][19][20][21] RBP-J or suppressor of hairless (SuH), the Drosophila homolog of RBP-J , is a known transcriptional repressor capable of regulating transcription through numerous cellular and viral promoters by binding to its cognate sequence within promoter regions.…”

A histone deacetylase corepressor complex regulates the Notch signal transduction pathway

“…Activation of Su(H) is thought to be dependent on a direct physical interaction with the Notch cytoplasmic domain. Homologs of these proteins have been described in Xenopus (Wettstein et al 1997), mouse (Matsunami et al 1989), and humans (Amakawa et al 1993) suggesting a high degree of evolutionary conservation. For example, the mammalian homolog of Su(H), CBF1/RBP-J , can bind and stimulate promoters of the mouse Hairy enhancer of split (HES-1) genes in the presence of vertebrate Notch (Jarriault et al 1995).…”

Identity of the β-Globin Locus Control Region Binding Protein HS2NF5 as the Mammalian Homolog of the Notch-regulated Transcription Factor Suppressor of Hairless

“…The sequences of two peptides from each of the 56-and 61-kDa forms were obtained. All four sequences were identical to the previously cloned murine homolog of the Drosophila transcription factor Su(H) (39,40), also known as CBF1 (41). The positions of the peptide sequences relative to the sequence of Drosophila Su(H) and murine CBF1 are shown in Fig.…”

“…A General Role for Notch Signaling in Hematopoietic Cells?-CBF1 was first purified from a pre-B-cell line, based on its binding to the J recombination signal (41). It was later revealed that a CBF1-binding site was created by the concatamerization of this sequence (42).…”

“…Since HS2NF5 had an apparently unique DNA binding specificity, a variable distribution in cell lines, and was the major activity that bound with high affinity to a functionally important region of HS2, we chose to purify HS2NF5. Here, we describe the identification of two forms of HS2NF5 as the previously cloned transcription factor known as Su(H) in Drosophila (39,40), and RBPJ or CBF1 2 in mammals (41,42). As Su(H) and CBF1 are critical developmental regulators and downstream targets of the Notch signaling pathway, we discuss a potential role for Notch signaling in LCR activity and hematopoiesis.…”