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  1.  review article 
    (2009) Kee BL. E and ID proteins branch out. Nat. Rev. Immunol., 9(3):175-84.
    E and inhibitor of DNA binding (ID) proteins are transcriptional regulators that function in many developmental processes in vertebrates and invertebrates. One subset of E proteins, the E2A proteins, have a central role in the transcriptional regulatory networks that promote commitment to and differentiation of the B- and T-cell lineages, and their function in these lineages is modulated by ID proteins. In this Review, I discuss recent studies that reveal a more extensive role for E and ID proteins in the transcriptional networks that drive the differentiation of many lymphoid lineages, as well as new functions for these proteins in haematopoietic stem cells and their multipotent, but lymphoid-primed, progeny.
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  2.  review article 
    (2007) Nutt SL, Kee BL. The transcriptional regulation of B cell lineage commitment. Immunity, 26(6):715-25.
    The expression of lineage-associated genes, as well as the survival and expansion of committed B cell progenitors, is controlled by multiple transcriptional regulators and growth-factor receptors. Whereas certain DNA-binding proteins, such as Ikaros and PU.1, are required primarily for the formation of more primitive lymphoid progenitors, other factors such as E2A and EBF1 have more direct roles in specifying the B cell-specific gene-expression program. Further, Pax5 functions to promote B cell commitment by repressing lineage-inappropriate gene expression and reinforcing B cell-specific gene expression. In this review, we focus on recent studies that have revealed that instead of a simple transcriptional hierarchy, efficient B cell commitment and differentiation requires the combinatorial activity of multiple transcription factors in a complex gene regulatory network.
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  3.  review article 
    (2000) Kee BL, Quong MW, Murre C. E2A proteins: essential regulators at multiple stages of B-cell development. Immunol. Rev., 175:138-49.
    The development of mature B lymphocytes from multipotent progenitor cells requires the co-ordinated activities of a number of transcriptional regulatory proteins. The transcription factors encoded by the E2A gene are required for the development of committed B-lineage cells and regulate the expression of essential B-lineage genes at multiple stages of differentiation and activation. In this review we discuss the evidence that the E2A gene products function in the regulation of 1) transcription factors required for B-lineage determination, 2) essential proteins involved in pro-B and pre-B-cell development, 3) accessibilty and recombination of the IgH and IgL chain loci, and 4) isotype switching in activated, mature B lymphocytes.
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  4. (2009) Gupta A, Hou R, Liu L, Hiroyasu S, Hadix JA, Huggins GS, Sibinga NE. Daxx inhibits muscle differentiation by repressing E2A-mediated transcription. J. Cell. Biochem., 107(3):438-47.
    The basic helix-loop-helix (HLH) E2A transcription factors bind to DNA as homodimers or as heterodimers formed with other basic HLH factors, activate gene expression, and promote differentiation of muscle, lymphoid, neuronal, and other cell types. These E2A functions can be inhibited by the Id proteins, HLH factors that sequester E2A in non-DNA binding dimers. Here we describe the direct interaction of E2A with Daxx, a broadly expressed non-HLH protein previously associated with apoptosis and transcriptional repression. Daxx inhibits E2A function, but not via an Id-like mechanism; rather, it recruits histone deacetylase activity to E2A-dependent promoters. Increased Daxx expression during muscle differentiation inhibits E2A-dependent expression of key myogenic genes and reduces myotube formation, while decreased Daxx expression promotes myotube formation. These results identify a new mechanism for limiting E2A activity and establish a link between Daxx-mediated gene regulation and control of cellular differentiation.
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  5. (2009) Beck K, Peak MM, Ota T, Nemazee D, Murre C. Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci. J. Exp. Med., 206(10):2271-84.
    The E2A gene products, E12 and E47, are critical regulators of B cell development. However, it remains elusive whether E12 and E47 have overlapping and/or distinct functions during B lymphopoiesis. We have generated mice deficient for either E12 or E47 and examined their roles in B cell maturation. We show that E47 is essential for developmental progression at the prepro-B cell stage, whereas E12 is dispensable for early B cell development, commitment, and maintenance. In contrast, both E12 and E47 play critical roles in pre-B and immature B cells to promote immunoglobulin lambda (Ig lambda) germline transcription as well as Ig lambda VJ gene rearrangement. Furthermore, we show that E12 as well as E47 is required to promote receptor editing upon exposure to self-antigen. We demonstrate that increasing levels of E12 and E47 act to induce Ig lambda germline transcription, promote trimethylated lysine 4 on histone 3 (H3) as well as H3 acetylation across the J lambda region, and activate Ig lambda VJ gene rearrangement. We propose that in the pre-B and immature B cell compartments, gradients of E12 and E47 activities are established to mechanistically regulate the sequential rearrangement of the Ig light chain genes.
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  6. (2009) Jones ME, Zhuang Y. Regulation of V(D)J recombination by E-protein transcription factors. Adv. Exp. Med. Biol., 650:148-56.
    Extensive study of the E-proteins E2A and HEB duringlymphocyte development has revealed various functions for these bHLH transcription factors in regulating V(D)J recombination in both B- and T-cells. The study of E-proteins in mammals began with the identification of E2A by its ability to bind immunoglobulin heavy and light chain enhancers. Subsequent analysis has identified numerous roles for E2A and HEB at the immunoglobulin and T-cell receptor loci. E-protein targets also include the rag genes and other factors critical for recombination and for regulation of the developmental windows when cells undergo recombination. E-proteins appear to be master regulators that coordinate antigen receptor gene rearrangement and expression. This chapter focuses on how E-proteins regulate V(D)J recombination by activating transcription, initiating rearrangement and driving differentiation during B- and T-cell development.
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  7. (2009) Jones ME, Kondo M, Zhuang Y. A tamoxifen inducible knock-in allele for investigation of E2A function. BMC Dev. Biol., 9:51.
    ABSTRACT: BACKGROUND: E-proteins are transcription factors important for the development of a variety of cell types, including neural, muscle and lymphocytes of the immune system. E2A, the best characterized E-protein family member in mammals, has been shown to have stage specific roles in cell differentiation, lineage commitment, proliferation, and survival. However, due to the complexity of E2A function, it is often difficult to separate these roles using conventional genetic approaches. Here, we have developed a new genetic model for reversible control of E2A protein activity at physiological levels. This system was created by inserting a tamoxifen-responsive region of the estrogen receptor (ER) at the carboxyl end of the tcfe2a gene to generate E2AER fusion proteins. We have characterized and analyzed the efficiency and kinetics of this inducible E2AER system in the context of B cell development. RESULTS: B cell development has been shown previously to be blocked at an early stage in E2A deficient animals. Our E2AER/ER mice demonstrated this predicted block in B cell development, and E2AER DNA binding activity was not detected in the absence of ligand. In vitro studies verified rapid induction of E2AER DNA binding activity upon tamoxifen treatment. While tamoxifen treatment of E2AER/ER mice showed inefficient rescue of B cell development in live animals, direct exposure of bone marrow cells to tamoxifen in an ex vivo culture was sufficient to rescue and support early B cell development from the pre-proB cell stage. CONCLUSION: The E2AER system provides inducible and reversible regulation of E2A function at the protein level. Many previous studies have utilized over-expression systems to induce E2A function, which are complicated by the toxicity often resulting from high levels of E2A. The E2AER model instead restores E2A activity at an endogenous level and in addition, allows for tight regulation of the timing of induction. These features make our E2AER ex vivo culture system attractive to study both immediate and gradual downstream E2A-mediated events.
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  8. (2008) Ravanpay AC, Olson JM. E protein dosage influences brain development more than family member identity. J. Neurosci. Res., 86(7):1472-81.
    Loss-of-function studies have revealed the role of many basic helix-loop-helix (bHLH) transcription factors at specific points during development; however, the role of E proteins in the development of the nervous system has not been experimentally addressed. E proteins have been speculated to interact selectively with class II bHLH factors to form different neurogenic complexes. In this study, using coimmunoprecipitation in a culture model of neurogenesis (P19 cells), we show that E proteins E12, HEB, and E2-2 interact with neuroD2. Using electrophoretic mobility shift assay and P19 cell culture, we show that these heterodimers bind a neuroD2 preferred E box and induce neurogenesis equally well. We examine the mRNA levels of the three E proteins at 10 time points during brain development and show that E protein gene expression is regulated such that at certain times during development selective interaction between neuroD2 and a single E protein (HEB) is a possibility. This led us to study the brains of HEB and E2A knockout mice, which manifest no gross neuroanatomical, cellular, or behavioral deficits. These findings, together with homology in the primary peptide sequence of E proteins, suggest functional compensation among E proteins during development of the nervous system.
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  9. (2007) Sun L, Trausch-Azar JS, Ciechanover A, Schwartz AL. E2A protein degradation by the ubiquitin-proteasome system is stage-dependent during muscle differentiation. Oncogene, 26(3):441-8.
    The E2A proteins are basic helix-loop-helix transcription factors that regulate proliferation and differentiation in many cell types. In muscle cells, the E2A proteins form heterodimers with muscle regulatory factors such as MyoD, which then bind to DNA and regulate the transcription of target genes essential for muscle differentiation. We now demonstrate that E2A proteins are primarily localized in the nucleus in both C2C12 myoblasts and myotubes, and are degraded by the ubiquitin proteasome system evidenced by stabilization following treatment with the proteasome inhibitor, MG132. During the differentiation from myoblast to myotube, the cellular abundance of E2A proteins is relatively unaltered, despite significant changes (each approximately 5-fold) in the relative rates of protein synthesis and protein degradation via the ubiquitin-proteasome system. The rate of ubiquitin-proteasome-mediated E2A protein degradation depends on the myogenic differentiation state (t 1/2 approximately 2 h in proliferating myoblasts versus t 1/2 > 10 h in differentiated myotubes), and is also associated with cell cycle in non-muscle cells. Our findings reveal an important role for both translational and post-translational regulatory mechanisms in mediating the complex program of muscle differentiation determined by the E2A proteins.
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  10. (2004) Greenbaum S, Lazorchak AS, Zhuang Y. Differential functions for the transcription factor E2A in positive and negative gene regulation in pre-B lymphocytes. J. Biol. Chem., 279(43):45028-35.
    The transcription factors encoded by the E2A gene have been shown to play essential roles in the initiation and progression of lymphocyte development. However, there is still a lack of comprehensive understanding of E2A downstream genes in B-cell development. We previously developed a gene tagging-based chromatin immunoprecipitation (ChIP) system to directly evaluate E2A target genes in B-cell development. Here, we have improved this ChIP strategy and used it in conjunction with microarray analysis on E2A-deficient pre-B-cell lines to determine E2A target genes in lymphocyte development. Both microarray data and ChIP studies confirmed that E2A directly controls IgH gene expression. The microarray assay also revealed genes that were significantly up-regulated after E2A disruption. ChIP analysis showed that E2A was most likely to be directly involved in repression of some of these target genes such as Nfil3 and FGFR2. An inducible E2A reconstitution system further demonstrated that E2A-mediated repression of Nfil3 and FGFR2 was reversible. Collectively, these findings indicate that E2A is a positive regulator for one set of genes and a negative regulator for another set of genes in developing B lymphocytes.
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  11. (2004) Huang Z, Nie L, Xu M, Sun XH. Notch-induced E2A degradation requires CHIP and Hsc70 as novel facilitators of ubiquitination. Mol. Cell. Biol., 24(20):8951-62.
    E2A transcription factors, E12 and E47, are important regulators of lymphocyte development. Notch signaling pathways have been shown to regulate E2A function by accelerating the degradation of E2A proteins through a mitogen-activated protein kinase-dependent and ubiquitin-mediated pathway. To further understand the mechanism underlying E2A ubiquitination and degradation, we conducted a yeast two-hybrid screen and identified the carboxyl terminus of Hsc70-interacting protein (CHIP) as an E47 binding protein. Here, we show that CHIP associates with E2A proteins in vivo and that overexpression of CHIP induces E47 degradation in a phosphorylation-dependent manner. Conversely, knocking down CHIP with small interfering RNA alleviates Notch-induced E47 degradation. CHIP binds E47 through the E protein homology domains 2 and 3 (EHD2 and EHD3). This interaction between CHIP and E47 is independent of the U-box domain with E3 ubiquitin ligase activity but requires the chaperone binding tetratricopeptide repeats domain. The ability of CHIP to induce E47 ubiquitination and degradation correlates with its ability to bind E47. We propose that CHIP, together with its partner Hsc70, forms a preubiquitination complex (PUC) with E47 and Skp2, thus facilitating the interaction between E47 and Skp2. CHIP also associates with Cul1, which introduces PUC to the SCF E3 ligase complex, responsible for E47 ubiquitination. Therefore, CHIP plays a crucial role in the ubiquitination and degradation of E2A proteins.
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  12. (2003) Bradney C, Hjelmeland M, Komatsu Y, Yoshida M, Yao TP, Zhuang Y. Regulation of E2A activities by histone acetyltransferases in B lymphocyte development. J. Biol. Chem., 278(4):2370-6.
    Genetic studies have demonstrated that the basic helix-loop-helix protein E2A is an essential transcription factor in B lymphocyte lineage commitment and differentiation. However, the mechanism underlying E2A-mediated transcription regulation is not fully understood. Here, we investigated the physical and genetic interactions between E2A and co-activators histone acetyltransferases (HATs) in B cells. Gel filtration analysis of human pre-B cell nuclear extract showed that E2A co-elutes with the HATs p300, CBP, and PCAF. A co-immunoprecipitation assay further demonstrated that a fraction of endogenous E2A proteins is associated with each of the three HATs. We show that these HATs acetylate E2A in vitro, enhance E2A-mediated transcription activity, and promote nuclear retention of E2A proteins. A catalytic mutation of p300 completely abrogates the ability of p300 to acetylate E2A and to promote E2A nuclear retention in 293T cells. A breeding test between E2A heterozygous mice and p300 heterozygous mice demonstrated that these two genes interact for proper B cell development. Collectively, these results suggest that E2A and HATs collaboratively regulate B cell development.
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  13. (2002) Sigvardsson M, Clark DR, Fitzsimmons D, Doyle M, Akerblad P, Breslin T, Bilke S, Li R, Yeamans C, Zhang G, Hagman J. Early B-cell factor, E2A, and Pax-5 cooperate to activate the early B cell-specific mb-1 promoter. Mol. Cell. Biol., 22(24):8539-51.
    Previous studies have suggested that the early-B-cell-specific mb-1(Igalpha) promoter is regulated by EBF and Pax-5. Here, we used in vivo footprinting assays to detect occupation of binding sites in endogenous mb-1 promoters at various stages of B-cell differentiation. In addition to EBF and Pax-5 binding sites, we detected occupancy of a consensus binding site for E2A proteins (E box) in pre-B cells. EBF and E box sites are crucial for promoter function in transfected pre-B cells, and EBF and E2A proteins synergistically activated the promoter in transfected HeLa cells. Other data suggest that EBF and E box sites are less important for promoter function at later stages of differentiation, whereas binding sites for Pax-5 (and its Ets ternary complex partners) are required for promoter function in all mb-1-expressing cells. Using DNA microarrays, we found that expression of endogenous mb-1 transcripts correlates most closely with EBF expression and negatively with Id1, an inhibitor of E2A protein function, further linking regulation of the mb-1 gene with EBF and E2A. Together, our studies demonstrate the complexity of factors regulating tissue-specific transcription and support the concept that EBF, E2A, and Pax-5 cooperate to activate target genes in early B-cell development.
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  14. (1999) Massari ME, Grant PA, Pray-Grant MG, Berger SL, Workman JL, Murre C. A conserved motif present in a class of helix-loop-helix proteins activates transcription by direct recruitment of the SAGA complex. Mol. Cell, 4(1):63-73.
    The class I helix-loop-helix (HLH) proteins, which include E2A, HEB, and E2-2, have been shown to be required for lineage-specific gene expression during T and B lymphocyte development. Additionally, the E2A proteins function to regulate V(D)J recombination, possibly by allowing access of variable region segments to the recombination machinery. The mechanisms by which E2A regulates transcription and recombination, however, are largely unknown. Here, we identify a novel motif, LDFS, present in the vertebrate class I HLH proteins as well as in a yeast HLH protein that is essential for transactivation. We provide both genetic and biochemical evidence that the highly conserved LDFS motif stimulates transcription by direct recruitment of the SAGA histone acetyltransferase complex.
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  15. (1997) Prabhu S, Ignatova A, Park ST, Sun XH. Regulation of the expression of cyclin-dependent kinase inhibitor p21 by E2A and Id proteins. Mol. Cell. Biol., 17(10):5888-96.
    The helix-loop-helix transcription factor E2A plays important roles not only in promoting cellular differentiation but also in suppressing cell growth. Id proteins, the inhibitors of E2A, have opposite effects on cell differentiation and growth. To understand the mechanisms by which E2A suppresses cell growth, we examined the role of E2A in regulating the expression of the cyclin-dependent kinase inhibitor p21CIP1/WAF1/SD11, which prevents cell cycle progression upon overexpression. By using transient-cotransfection assays of luciferase reporter constructs in HeLa cells, we have found that overexpression of E2A can transcriptionally activate the p21 gene. To identify the sequences that mediate this activation in the promoter of the p21 gene, we carried out mutational analyses. Out of the eight putative E2A-binding sequences (E1 to E8) in the promoter, the E1 to E3 sequences located close to the transcription start site are found to be essential. In addition, loss of the E boxes in the promoter also reduces p21 expression without cotransfection with E2A in HIT pancreatic cells, where the endogenous E2A-like activity is high. Furthermore, we have also shown that overexpression of E2A in 293T cells activates expression of the endogenous p21 gene at both the levels of mRNA and protein. In correlation with the finding that E47 overexpression leads to growth arrest in NIH 3T3 cells, we have shown that Id1 overexpression in NIH 3T3 cells accelerates cell growth and inhibits p21 expression. Taken together, these results provide insight into the mechanisms by which E2A and Id proteins control cell growth.
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  16. (1997) Kho CJ, Huggins GS, Endege WO, Hsieh CM, Lee ME, Haber E. Degradation of E2A proteins through a ubiquitin-conjugating enzyme, UbcE2A. J. Biol. Chem., 272(6):3845-51.
    The helix-loop-helix E2A proteins (E12 and E47) govern cellular growth and differentiation. To identify binding partners that regulate the function of these ubiquitous transcription factors, we screened for proteins that interacted with the C terminus of E12 by the yeast interaction trap. UbcE2A, a rat enzyme that is highly homologous to and functionally complements the yeast ubiquitin-conjugating enzyme UBC9, was identified and cloned. UbcE2A appears to be an E2A-selective ubiquitin-conjugating enzyme because it interacts specifically with a 54-amino acid region in E47-(477-530) distinct from the helix-loop-helix domain. In contrast, most of the UbcE2A protein is required for interaction with an E2A protein. The E2A proteins appear to be degraded by the ubiquitin-proteasome pathway because the E12 half-life of 60 min is extended by the proteasome inhibitor MG132, and E12 is multi-ubiquitinated in vivo. Finally, antisense UbcE2A reduces E12 degradation. By participating in the degradation of the E2A proteins, UbcE2A may regulate cell growth and differentiation.
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  17. (1996) Sloan SR, Shen CP, McCarrick-Walmsley R, Kadesch T. Phosphorylation of E47 as a potential determinant of B-cell-specific activity. Mol. Cell. Biol., 16(12):6900-8.
    The E2A gene encodes two basic helix-loop-helix proteins designated E12 and E47. Although these proteins are widely expressed, they are required only for the B-lymphocyte lineage where DNA binding is mediated distinctively by E47 homodimers. By studying the properties of deltaE47, an N-terminal truncation of E47, we provide evidence that phosphorylation may contribute to B-cell-specific DNA binding by E47. Two serines N terminal to the deltaE47 basic helix-loop-helix domain were found to be phosphorylated in a variety of cell types but were hypophosphorylated in B cells. Phosphorylating these serines in vitro inhibited DNA binding by deltaE47 homodimers but not by deltaE47-containing heterodimers, such as deltaE47:MyoD. These results argue that hypophosphorylation may be a prerequisite for activity of E47 homodimers in B cells, suggesting the use of an inductive (nonstochastic) step in early B-cell development.
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  18. (1993) Aronheim A, Shiran R, Rosen A, Walker MD. The E2A gene product contains two separable and functionally distinct transcription activation domains. Proc. Natl. Acad. Sci. U.S.A., 90(17):8063-7.
    The E2A gene encodes transcription factors of the helix-loop-helix (HLH) family which are implicated in cell-specific transcriptional control in several cell lineages, including pancreatic beta cells. In the present work, we show by deletion mapping of both the E2A protein itself and the Gal4-E2A fusion protein that the protein contains at least two distinct activation domains. One domain (located between amino acids 1 and 153) functions efficiently in a variety of mammalian cell lines. The second domain (located between amino acids 369 and 485) functions preferentially in pancreatic beta cell lines. The latter domain shows a pattern of heptad repeats of leucine residues characteristics of "leucine zipper" transcription factors; site-directed mutagenesis of leucines within this repeat led to substantial reductions in activity. The selective properties of this activation domain may contribute to cell-specific transcription directed by the E2A gene.
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  19. (1991) Sun XH, Copeland NG, Jenkins NA, Baltimore D. Id proteins Id1 and Id2 selectively inhibit DNA binding by one class of helix-loop-helix proteins. Mol. Cell. Biol., 11(11):5603-11.
    The DNA binding activities of some basic region and putative helix-loop-helix (bHLH)-containing transcriptional factors can be inhibited by the Id protein. Because Id contains the HLH motif for dimerization but not the basic amino acid region for DNA binding, heterodimers of Id with bHLH transcriptional factors may not bind to DNA. We have isolated and characterized the gene and cDNA clones for a new Id protein, designated Id2. The Id2 protein contains a helix-loop-helix motif similar to that of the previously described Id protein (referred to here as Id1), but the two proteins are different elsewhere. Id1 and Id2 are encoded by two unlinked genes, as shown by chromosome mapping. The two Id proteins have similar inhibitory activities. They selectively bind to and inhibit the function of one set of bHLH proteins, typified by E2A.E47 and E2B.m3, but not that of the other set, including TFE3, USF, and AP4. The Id proteins also homodimerize poorly. Expression of both Id genes is down-regulated during differentiation in a variety of cell types.
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  20. (1991) Sun XH, Baltimore D. An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers. Cell, 64(2):459-70.
    The kappa E2 sequence binding proteins, E12 and E47, are generated by alternative splicing of the E2A gene, giving closely related basic and helix-loop-helix structures crucial for DNA binding and dimerization. Measurements of dimerization constants and binding strengths to the optimal DNA sequence (the kappa E2 site or its near relatives) showed that E47 homodimers and MyoD heterodimers with E12 or E47 dimerized and bound avidly, but E12 homodimerized efficiently and bound to DNA poorly; MyoD homodimerized poorly and bound strongly. An inhibitory domain N-terminal to the basic region of E12 prevents E12 homodimers but not E12/MyoD heterodimers from binding to DNA. Thus, E47 binds to DNA both as a heterodimer with MyoD and as a homodimer, while E12 and MyoD bind to DNA efficiently only as heterodimers.
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  21. (1990) Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell, 61(1):49-59.
    We have isolated a cDNA clone encoding a novel helix-loop-helix (HLH) protein, Id. Id is missing the basic region adjacent to the HLH domain that is essential for specific DNA binding in another HLH protein, MyoD. An in vitro translation product of Id can associate specifically with at least three HLH proteins (MyoD, E12, and E47) and attenuate their ability to bind DNA as homodimeric or heterodimeric complexes. Id is expressed at varying levels in all cell lines tested. In three cell lines that can be induced to undergo terminal differentiation, Id RNA levels decrease upon induction. Transfection experiments indicate that over-expression of Id inhibits the trans-activation of the muscle creatine kinase enhancer by MyoD. Based on these findings, we propose that HLH proteins lacking a basic region may negatively regulate other HLH proteins through the formation of nonfunctional heterodimeric complexes.
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  22. (1989) Murre C, McCaw PS, Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell, 56(5):777-83.
    Two cDNAs were isolated whose dimerized products bind specifically to a DNA sequence, kappa E2, located in the immunoglobulin kappa chain enhancer. Both cDNAs share a region of extensive identity to the Drosophila daughterless gene and obvious similarity to a segment in three myc proteins, MyoD, and members of the Drosophila achaete-scute and twist gene family. The homologous regions have the potential to form two amphipathic helices separated by an intervening loop. Remarkable is the stringent conservation of hydrophobic residues present in both helices. We demonstrate that this new motif plays a crucial role in both dimerization and DNA binding.
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