Erythropoietin Stimulates Transcription of the TAL1/SCL Gene and Phosphorylation of Its Protein Products

Activation of the TAL1 (or SCL) gene, originally identified through its involvement by a recurrent chromosomal translocation, is the most frequent molecular lesion recognized in T-cell acute lymphoblastic leukemia. The protein products of this gene contain the basic-helix-loop-helix motif characteristic of a large family of transcription factors that bind to the canonical DNA sequence CANNTG as protein heterodimers. TAL1 expression by erythroid cells in vivo and in chemical-induced erythroleukemia cell lines in vitro suggested the gene might regulate aspects of erythroid differentiation. Since the terminal events of erythropoiesis are controlled by the glycoprotein hormone erythropoietin (Epo), we investigated whether the expression or activity of the TAL1 gene and its protein products were affected by Epo in splenic erythroblasts from mice infected with an anemia-inducing strain of Friend virus (FVA cells). Epo elicited a rapid, dose-related increase in TAL1 mRNA by increasing transcription of the gene and stabilizing one of its mRNAs. An Epo-inducible TAL1 DNA binding activity was identified in FVA cell nuclear extracts that subsequently decayed despite accumulating mRNA and protein. Induction of DNA binding activity was associated temporally with Epo-induced phosphorylation of nuclear TAL1 protein. These results indicate that Epo acts at both transcriptional and post-transcriptional levels on the TAL1 locus in Friend virus-induced erythroblasts and establish a link between Epo signaling mechanisms and a member of a family of transcription factors involved in the differentiation of diverse cell lineages. Activation of the TAL1 (or SCL) gene, originally identified through its involvement by a recurrent chromosomal translocation, is the most frequent molecular lesion recognized in T-cell acute lymphoblastic leukemia. The protein products of this gene contain the basic-helix-loop-helix motif characteristic of a large family of transcription factors that bind to the canonical DNA sequence CANNTG as protein heterodimers. TAL1 expression by erythroid cells in vivo and in chemical-induced erythroleukemia cell lines in vitro suggested the gene might regulate aspects of erythroid differentiation. Since the terminal events of erythropoiesis are controlled by the glycoprotein hormone erythropoietin (Epo), we investigated whether the expression or activity of the TAL1 gene and its protein products were affected by Epo in splenic erythroblasts from mice infected with an anemia-inducing strain of Friend virus (FVA cells). Epo elicited a rapid, dose-related increase in TAL1 mRNA by increasing transcription of the gene and stabilizing one of its mRNAs. An Epo-inducible TAL1 DNA binding activity was identified in FVA cell nuclear extracts that subsequently decayed despite accumulating mRNA and protein. Induction of DNA binding activity was associated temporally with Epo-induced phosphorylation of nuclear TAL1 protein. These results indicate that Epo acts at both transcriptional and post-transcriptional levels on the TAL1 locus in Friend virus-induced erythroblasts and establish a link between Epo signaling mechanisms and a member of a family of transcription factors involved in the differentiation of diverse cell lineages. The TAL1 (also known as SCL and TCL5) gene was originally identified through its location at a chromosome breakpoint in patients with T-cell acute lymphoblastic leukemia (1Begley C.G. Aplan P.D. Denning S.M. Haynes B.F. Waldmann T.A. Kirsch I.R. Proc. Natl. Acad. Sci. U. S. A. 1989; 86: 10128-10132Crossref PubMed Scopus (311) Google Scholar, 2Chen Q. Cheng J.-T. Tsai L.-H. Schneider N. Buchanan G. Carroll A. Crist W. EMBO J. 1990; 9: 415-424Crossref PubMed Scopus (278) Google Scholar, 3Finger L.R. Kagan J. Christopher G. Kurtzberg J. Hershfield M.S. Nowell P.C. Croce C.M. Proc. Natl. Acad. Sci. U. S.A. 1989; 86: 5039-5043Crossref PubMed Scopus (205) Google Scholar). Although involved in reciprocal translocations with the T-cell receptor-α/δ and, in one case, -β locus (4Fitzgerald T.J. Neale G.A.M. Raimondi S.C. Goorha R.M. Blood. 1991; 78: 2686-2695Crossref PubMed Google Scholar), the gene is more frequently affected by interstitial deletions upstream of its coding region which result in the head-to-tail fusion of the TAL1 and SIL (for SCL interrupting locus) genes (5Aplan P.D. Lombardi D.P. Ginsberg A.M. Cossman J. Bertness V.L. Kirsch I.R. Science. 1990; 250: 1426-1429Crossref PubMed Scopus (241) Google Scholar, 6Brown L. Cheng J.-T. Chen Q. Siciliano M.J. Crist W. Buchanan G. Baer R. EMBO J. 1990; 9: 3343-3351Crossref PubMed Scopus (294) Google Scholar, 7Bernard O. Lecointe N. Jonveaux P. Souyri M. Mauchauffe M. Berger R. Larsen C.J. Oncogene. 1991; 6: 1477-1488PubMed Google Scholar). These chromosomal abnormalities do not generally alter the gene's coding potential and likely contribute to leukemogenesis through inappropriate expression of the rearranged allele (8Baer R. Cancer Biol. 1993; 4: 341-347PubMed Google Scholar, 9Goldfarb A.N. Greenberg J.M. Leuk. & Lymphoma. 1994; 12: 157-166Crossref PubMed Scopus (10) Google Scholar). Overall, deregulated TAL1 expression may occur in as many as 30% of individuals with T-cell acute lymphoblastic leukemia, making this the most frequent molecular lesion recognized in this disorder. The protein products of the TAL1 gene contain a dimerization motif characteristic of a large family of genes involved in the regulation of cell fate (10Garrell J. Campuzano S. BioEssays. 1991; 13: 493-498Crossref PubMed Scopus (77) Google Scholar, 11Kadesch T. Cell Growth Diff. 1993; 4: 49-55PubMed Google Scholar). This conserved domain was predicted to adopt a helix-loop-helix (HLH) 1The abbreviations used are: HLH, helix-loop-helix; bHLH, basic domain helix-loop-helix; MEL, murine erythroleukemia; Epo, erythropoietin; FVA, anemia-inducing strain of Friend virus; kb, kilobase(s); EMSA, electrophoretic mobility shift assay; EpoR, erythropoietin receptor. conformation in which two amphipathic helices are separated by a less structured loop region of varying length (12Murre C. McCaw P.S. Baltimore D. Cell. 1989; 56: 777-783Abstract Full Text PDF PubMed Scopus (2013) Google Scholar). The HLH motif promotes the formation of protein hetero- and homodimers, while an adjacent region enriched in basic amino acids and found in many of the proteins of this class mediates sequence-specific DNA binding (13Voronova A. Baltimore D. Proc. Natl. Acad. Sci. U. S. A. 1990; 87: 4722-4726Crossref PubMed Scopus (249) Google Scholar, 14Davis R.L. Cheng P.-F. Lassar A.B. Weintraub H. Cell. 1990; 60: 733-746Abstract Full Text PDF PubMed Scopus (584) Google Scholar, 15Lassar A.B. Davis R.L. Wright W.E. Kadesch T. Murre C. Voronova A. Baltimore D. Weintraub H. Cell. 1991; 66: 305-315Abstract Full Text PDF PubMed Scopus (718) Google Scholar). The basic domain-HLH (bHLH) proteins, including TAL1 (16Hsu H.-L. Cheng J.-T. Chen Q. Baer R. Mol. Cell. Biol. 1991; 11: 3037-3042Crossref PubMed Scopus (143) Google Scholar, 17Hsu H.-L. Wadman I. Baer R. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 3181-3185Crossref PubMed Scopus (106) Google Scholar), bind as dimers to a canonical sequence CANNTG termed the E-box and function as transcriptional regulators. Distinct subgroups of HLH genes can be recognized on the basis of sequence homology, pattern of expression, and function. Four bHLH proteins, of which MyoD is the prototype, are expressed in developing muscle and share the ability to induce myogenic differentiation when expressed in certain cell lines (18Weintraub H. Tapscott S.J. Davis R.L. Thayer M.J. Adam M.A. Lassar A.B. Miller A.D. Proc. Natl. Acad. Sci. U. S. A. 1989; 86: 5434-5438Crossref PubMed Scopus (787) Google Scholar, 19Weintraub H. Davis R. Tapscott S. Thayer M. Krause M. Benezra R. Blackwell T.K. Science. 1991; 251: 761-766Crossref PubMed Scopus (1310) Google Scholar). The three genes TAL1, TAL2, and LYL-1 show greater than 80% identity within their basic and HLH domains and share an additional similarity in that each was isolated as a result of its involvement in a human leukemia (8Baer R. Cancer Biol. 1993; 4: 341-347PubMed Google Scholar). The recently identified bHLH-EC2 gene also shows considerable sequence homology to and overlaps with TAL1 in its expression (20Quertermous E.E. Hidai H. Blanar M.A. Quertermous T. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 7066-7070Crossref PubMed Scopus (51) Google Scholar). TALI RNA has been detected in megakaryocytic, erythroid, and mast cell lines (21Green A.R. Salvaris E. Begley C.G. Oncogene. 1991; 6: 475-479PubMed Google Scholar, 22Visvader J. Begley C.G. Adams J.M. Oncogene. 1991; 6: 187-194PubMed Google Scholar, 23Green A.R. Lints T. Visvader J. Harvey R. Begley C.G. Oncogene. 1992; 7: 653-660PubMed Google Scholar) and by in situ hybridization in human megakaryocytes, erythroblasts, and basophilic granulocytes (24Mouthon M.-A. Bernard O. Mitjavila M.-T. Romeo P.-H. Vainchenker W. Mathieu-Mahul D. Blood. 1993; 81: 647-655Crossref PubMed Google Scholar). Endothelial cells (25Hwang L.-Y. Siegelman M. Davis L. Oppenheimer-Marks N. Baer R. Oncogene. 1993; 8: 3043-3046PubMed Google Scholar) and neurons (23Green A.R. Lints T. Visvader J. Harvey R. Begley C.G. Oncogene. 1992; 7: 653-660PubMed Google Scholar) have also been found to express TAL1 RNA and protein, and studies of its expression during embryogenesis suggest the gene may have actions in vascular, neural, and hematopoietic development (26Kallianpur A.R. Jordan J.E. Brandt S.J. Blood. 1994; 83: 1200-1208Crossref PubMed Google Scholar). Considerable evidence suggests that TAL1 regulates aspects of erythroid differentiation. TAL1 RNA and protein are expressed in embryonic and adult erythroid progenitors (21Green A.R. Salvaris E. Begley C.G. Oncogene. 1991; 6: 475-479PubMed Google Scholar, 23Green A.R. Lints T. Visvader J. Harvey R. Begley C.G. Oncogene. 1992; 7: 653-660PubMed Google Scholar, 26Kallianpur A.R. Jordan J.E. Brandt S.J. Blood. 1994; 83: 1200-1208Crossref PubMed Google Scholar) and in murine erythroleukemia (MEL) cell lines, increasing significantly with hexamethylene bisacetamide- or Me2SO-induced differentiation (21Green A.R. Salvaris E. Begley C.G. Oncogene. 1991; 6: 475-479PubMed Google Scholar, 22Visvader J. Begley C.G. Adams J.M. Oncogene. 1991; 6: 187-194PubMed Google Scholar, 27Aplan P.D. Nakahara K. Orkin S.H. Kirsch I.R. EMBO J. 1992; 11: 4073-4081Crossref PubMed Scopus (203) Google Scholar). the expression of TAL1 promotes the differentiation of lines in the of while of TAL1 expression and hexamethylene differentiation P.D. Nakahara K. Orkin S.H. Kirsch I.R. EMBO J. 1992; 11: 4073-4081Crossref PubMed Scopus (203) Google Scholar). Since the terminal events of erythropoiesis are controlled by the glycoprotein hormone erythropoietin (Epo), suggested that the expression of the TAL1 gene or the activity of its protein products might be by this the of Epo on TAL1 mRNA and protein expression we have used erythroblasts from the of mice infected with an anemia-inducing strain of Friend virus (FVA cells). to lines, cells show an on Epo their in and the is M.J. Science. 1990; PubMed Scopus Google Scholar). the of Epo, FVA cells a of differentiation a of including nuclear with the formation of M.J. J. Cell. Scopus Google Scholar). This cell has been with to on M.J. Mol. Cell. Biol. PubMed Scopus Google Scholar), M.J. J. Cell Biol. 1989; PubMed Scopus Google Scholar), and cell M.J. Science. 1990; PubMed Scopus Google Scholar), and an of erythroid differentiation. indicate that and at both transcriptional and post-transcriptional on the TAL1 locus in establish a link between signaling by this hematopoietic and a family of transcription factors many of have been to cell mice of of were of an anemia-inducing strain of Friend virus by The were and erythroblasts from cell by at through a of to as M.J. J. Cell. Scopus Google Scholar). erythroblasts were in with 30% and with the of human Epo were at the of and with to RNA was isolated from erythroblasts a P. N. PubMed Scopus Google Scholar). RNA were by in and by to and were at in and were at with in the and with at at and at were to and the by RNA was to RNA a of the as A. Blood. 1991; 78: PubMed Google Scholar). from were used in the RNA both the and TAL1 as a function of Epo in RNA levels in cells were by a of the TAL1 was used as This region not contain the conserved basic and HLH domains to potential to HLH The was an of the coding sequence of murine A.D. Orkin S.H. 1989; PubMed Scopus Google Scholar), the was a of of murine sequence R. Davis R.L. D. Weintraub H. Cell. 1990; Full Text PDF PubMed Scopus Google Scholar), and the LYL-1 was a of murine LYL-1 sequence J. Begley C.G. Adams J.M. Oncogene. 1991; 6: 187-194PubMed Google Scholar). were with by PubMed Scopus Google Scholar). were isolated from erythroblasts at the a as M.J. Mol. Cell. Biol. PubMed Scopus Google Scholar) and at in a and vitro transcription was as J. Biol. 1990; Full Text PDF PubMed Google Scholar) and of at the RNA was with and with and with and and in the by were at at in and DNA and in the RNA to an of was at and in at and at with three The TAL1 used hybridization was used in nuclear The was a of the the coding region M. A. P. A. J. Biol. Full Text PDF PubMed Google Scholar). were to and the by of RNA to in was and not in from were used to the increase in transcriptional as a function of Epo from that at of were by a of FVA cells were with or Epo, which was at a of studies that this of was to transcription in FVA cells during the A. Blood. 1991; 78: PubMed Google Scholar). RNA was isolated at to and by hybridization as The were by and the of mRNA from was expressed both and cells as a function of of to A. Blood. 1991; 78: PubMed Google Scholar). was used to the of the and in a expressed the amino acids of murine TAL1 has been (26Kallianpur A.R. Jordan J.E. Brandt S.J. Blood. 1994; 83: 1200-1208Crossref PubMed Google Scholar). was from to on protein and used at an PubMed Scopus Google Scholar) of FVA cell nuclear protein as electrophoretic mobility shift were on and to were with as E. D. Scholar) and binding detected by were by and from were used in the TAL1 protein as a function of Epo The of TAL1 protein levels in was at each and from that at of a of were by a extracts were from FVA cells the of R.M. 11: PubMed Scopus Google Scholar) with FVA cells were in a and and isolated with a were at and in and The extracts were on by at and in at of the were with by and with nuclear extracts in with or the at in a binding of and in a of mobility shift were as R.L. Cheng P.-F. Lassar A.B. Weintraub H. Cell. 1990; 60: 733-746Abstract Full Text PDF PubMed Scopus (584) Google Scholar). were to and by The of the of each of with the are: were with and at were at a of in with and Epo the cells were and with and nuclear and extracts as of an of were in and to which or was The was at and isolated with protein E. D. Scholar). were in and on were by of FVA cells with Epo in in the levels of both the and TAL1 within of The was at with a increase RNA of and the and to that at the of increase in TAL1 mRNA was the of Epo in to with at greater than was detected at Epo of TAL1 mRNA in RNA was from FVA cells in the or of Epo the and to of were by from is expressed as a function of in Epo the and TAL1 mRNAs. The of in between and cells is by the and TALI mRNA was detected in erythroblasts to and was at levels to in The of cells to in the of Epo M.J. Science. 1990; PubMed Scopus Google Scholar) their The increase in TAL1 in FVA cell not a in transcription levels of mRNA expressed in many of the cell as TAL1, not increase at of and that of the HLH gene LYL-1 was not affected by Epo The of Epo on TAL1 transcription was in nuclear studies with the results of transcription of the TAL1 gene was detected in FVA cells at the of TAL1 transcription a within the of and the at of Epo was on transcription in the of with of mRNA levels in FVA cells during this A. Blood. 1991; 78: PubMed Google Scholar). These results indicate that of TAL1 results in from an increase in transcription of the whether the Epo-induced increase in levels of TAL1 also in their TAL1 was by in with at a to transcription A. Blood. 1991; 78: PubMed Google Scholar). The two of TAL1 which in their and C.G. Visvader J. A.R. Aplan P.D. D. Kirsch I.R. Proc. Natl. Acad. Sci. U. S. A. 1991; PubMed Scopus Google Scholar), were found to have of FVA cells with Epo significantly affected the of the of the TAL1 in a in the from to The of the was by Epo with the in both the and of RNA also to Epo-induced of TALI mRNA in Friend virus-induced TAL1 protein was by to of TAL1 proteins with molecular of in by as by in cells the increase in and TAL1 protein with a molecular of was expressed in at and by This protein has been in and erythroleukemia cell lines Baer R. Oncogene. 1993; 8: Google Scholar, A.R. A. Begley C.G. N. 1994; 8: Google Scholar), has not been found to in of proteins were detected with The molecular of TAL1 the were in FVA than in cells that or more of the proteins occur in Since the of this transcription are not two were used as in mobility shift of TAL1 DNA binding was from the to which TAL1 been to bind as a with the and protein products of the gene (16Hsu H.-L. Cheng J.-T. Chen Q. Baer R. Mol. Cell. Biol. 1991; 11: 3037-3042Crossref PubMed Scopus (143) Google Scholar). The was identified by a as a sequence DNA binding H.-L. L. W. Wright W.E. Mol. Cell. Biol. 1994; PubMed Scopus Google Scholar). the a was of FVA cell nuclear extracts with that was not in the of or with the of a in the motif was by not by or to the bHLH protein LYL-1 (26Kallianpur A.R. Jordan J.E. Brandt S.J. Blood. 1994; 83: 1200-1208Crossref PubMed Google Scholar) the of TAL1 protein in the less was also with the that to the as that of the was by in to the was by of extracts with TALI DNA binding activity within of of Epo to subsequently despite the of DNA binding activity in the of Epo, to be both as as Epo-inducible in FVA cell was also identified when FVA cell nuclear extracts were with the sequence as Although additional were with this not of which sequence-specific the most was affected by extracts with this was to the that was to the The of Epo on TAL1 DNA binding activity with the sequence was generally to that the that binding activity and The between TAL1 protein and DNA binding with the to whether the TAL1 protein products might be at a in FVA TAL1 been to phosphorylation in cell lines Baer R. Oncogene. 1993; 8: Google Scholar, A.N. S. D. Greenberg J.M. Blood. 1992; PubMed Google Scholar, J.-T. Baer R. Mol. Cell. Biol. 1993; 13: PubMed Scopus Google Scholar), the of Epo on TAL1 protein phosphorylation was by of nuclear extracts from FVA cells with nuclear recognized by the was more in with cells proteins of and were also with TAL1 in FVA cell nuclear studies that phosphorylation of within of and with results extracts were by or by protein This was to a nuclear of TAL1 protein in that increase in TAL1 phosphorylation was when extracts or extracts were of TAL1 expression have that the gene is in erythroid progenitors and suggested its protein products have a in erythroid differentiation. T. A. K. A. M. Proc. Natl. Acad. Sci. U. S. A. 1993; PubMed Scopus Google Scholar) that Epo induce the of TAL1 in an cell to express the Epo of Friend virus-induced erythroblasts that TAL1 transcription is an to Epo results indicate that of the TAL1 gene is a of the signaling and suggest TAL1 may be involved in actions on erythroid of hexamethylene and on lines (21Green A.R. Salvaris E. Begley C.G. Oncogene. 1991; 6: 475-479PubMed Google Scholar, 27Aplan P.D. Nakahara K. Orkin S.H. Kirsch I.R. EMBO J. 1992; 11: 4073-4081Crossref PubMed Scopus (203) Google Scholar), in erythroblasts were on cells TAL1 mRNA and protein. These results be by TAL1 transcription been at of differentiation M.A. C.M. A.M. A.R. Oncogene. 1994; 9: Google Scholar) and with an increase in the of transcription or of an P.D. Begley C.G. Bertness M. A. J. Kirsch I.R. Cell. Biol. 1990; PubMed Scopus Google Scholar, C.G. L. S. Visvader J. A.R. 1994; PubMed Scopus Google Scholar, N. Bernard O. K. Larsen C.J. Romeo Mathieu-Mahul D. Oncogene. 1994; 9: Google Scholar). has been to the TAL1 in erythroid cells P.D. Begley C.G. Bertness M. A. J. Kirsch I.R. Cell. Biol. 1990; PubMed Scopus Google Scholar, N. Bernard O. K. Larsen C.J. Romeo Mathieu-Mahul D. Oncogene. 1994; 9: Google Scholar) and, as is also expressed in FVA cells to the of Epo, contribute to this of protein, actions to be by A.D. 1992; Google Scholar, D. J. Biol. 1993; Full Text PDF PubMed Google Scholar), have in an to TALI this is the that the erythroleukemia cell T. M. Blood. 1991; PubMed Google Scholar), which not express also to express TAL1 Epo is to of proteins, in FVA cells in of the of Epo to M.J. A. Blood. 1993; PubMed Google Scholar), that the expression of TAL1 mRNA and protein in of Epo have also the of a of cells less the the the of TAL1 expression in an Epo-induced increase in the or activity of the TAL1 protein products may be of the erythroid differentiation as suggested M. M. T. Blood. 1993; PubMed Google Scholar). The increase in TAL1 mRNA in FVA cells was a by an increase in the of protein in the while an TAL1 protein, from a of on the coding Baer R. Oncogene. 1993; 8: Google Scholar), was expressed Since has that at one RNA from which this protein be is in S. S. J. E. M. J. M. C. and S. J. this pattern of expression suggests that its or may be by a result of a transcriptional domain found in the protein L. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: PubMed Scopus Google Scholar) is while the dimerization and be Although the function of this TAL1 is not a of of transcriptional and with of expression, by the gene as a result of in P. Cell. 1992; Full Text PDF PubMed Scopus Google Scholar). TALI DNA binding activity with a in FVA cells than predicted by the more increase in TAL1 protein levels and while mRNA and protein This pattern of TAL1 protein, the or activity of its dimerization in the of or of The increase in DNA binding activity temporally with the of nuclear TAL1 the that phosphorylation might regulate this function. is known to the nuclear and of DNA and activity of a of transcription factors in T. M. Cell. 1992; Full Text PDF PubMed Scopus Google Scholar), and its on TAL1 function may be of TAL1 is by the protein in cell lines and cells J.-T. Baer R. Mol. Cell. Biol. 1993; 13: PubMed Scopus Google Scholar), which be predicted to occur also in to Epo M. N. J. Biol. 1991; Full Text PDF PubMed Google Scholar, J. J.M. Sci. 1994; Full Text PDF PubMed Scopus Google Scholar), and this was recently to increase the activity of the transcriptional domain H.-L. Baer R. Oncogene. 1994; 9: Google Scholar). The on and and, J.-T. Baer R. Mol. Cell. Biol. 1993; 13: PubMed Scopus Google indicate that additional are and suggest the TAL1 proteins can also be protein The results of indicate that TAL1 phosphorylation in Friend virus-induced erythroblasts, as cell lines and cells Baer R. Oncogene. 1993; 8: Google Scholar), on or class HLH proteins C. McCaw P.S. H. M. Lassar A.B. Weintraub H. Baltimore D. Cell. 1989; Full Text PDF PubMed Scopus Google Scholar), DNA as a that its DNA binding activity might also be through its binding The in TAL1 binding activity in FVA be by a in the of proteins, with which TAL1 has been to bind DNA H.-L. Wadman I. Baer R. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 3181-3185Crossref PubMed Scopus (106) Google Scholar), or to an increase in of DNA as the Although TAL1 was to with and Baltimore D. Mol. Cell. Biol. 1991; 11: PubMed Scopus Google Scholar, W. T. M. J. Biol. 1994; Full Text PDF PubMed Google Scholar), was to the binding of to Proc. Natl. Acad. Sci. U. S. A. 1994; 91: PubMed Scopus Google Scholar). The levels and with differentiation in lines R. Davis R.L. D. Weintraub H. Cell. 1990; Full Text PDF PubMed Scopus Google Scholar, Baltimore D. Mol. Cell. Biol. 1991; 11: PubMed Scopus Google Scholar, W. T. M. J. Biol. 1994; Full Text PDF PubMed Google Scholar), and mRNA not be detected at the of in FVA cells at in the of to be a less likely the in DNA binding activity in erythroid with erythroleukemia cell lines have suggested a function the TAL1 gene in erythroid differentiation (21Green A.R. Salvaris E. Begley C.G. Oncogene. 1991; 6: 475-479PubMed Google Scholar, 27Aplan P.D. Nakahara K. Orkin S.H. Kirsch I.R. EMBO J. 1992; 11: 4073-4081Crossref PubMed Scopus (203) Google Scholar). human and murine erythroid studies at the of the cell indicate that TAL1 mRNA and protein expression with terminal differentiation (24Mouthon M.-A. Bernard O. Mitjavila M.-T. Romeo P.-H. Vainchenker W. Mathieu-Mahul D. Blood. 1993; 81: 647-655Crossref PubMed Google Scholar, M.J. Cell. 1994; 78: Full Text PDF PubMed Scopus Google Scholar). results show that at the to of erythroid differentiation by FVA TAL1 and DNA binding activity at by the actions of the TAL1 gene products in erythroid differentiation to be studies establish a link between signaling by the hormone that the terminal events of erythropoiesis and a member of a transcription family involved in the differentiation of diverse cell lineages. Benezra the the on DNA binding and