Site-specific Acetylation of the Fetal Globin Activator NF-E4 Prevents Its Ubiquitination and Regulates Its Interaction with the Histone Deacetylase, HDAC1

Acetylation provides one mechanism by which the functional diversity of individual transcription factors can be expanded. This is valuable in the setting of complex multigene loci that are regulated by a limited number of proteins, such as the human β-globin locus. We have studied the role of acetylation in the regulation of the transcription factor NF-E4, a component of a protein complex that facilitates the preferential expression of the human γ-globin genes in fetal erythroid cells. We have shown that NF-E4 interacts directly with, as a the Acetylation of NF-E4 is a in the of the protein in functional Acetylation of NF-E4 the protein by This is expression in of a of the NF-E4 Acetylation of the NF-E4 the of the factor the that such as can individual transcription factor Acetylation provides one mechanism by which the functional diversity of individual transcription factors can be expanded. This is valuable in the setting of complex multigene loci that are regulated by a limited number of proteins, such as the human β-globin locus. We have studied the role of acetylation in the regulation of the transcription factor NF-E4, a component of a protein complex that facilitates the preferential expression of the human γ-globin genes in fetal erythroid cells. We have shown that NF-E4 interacts directly with, as a the Acetylation of NF-E4 is a in the of the protein in functional Acetylation of NF-E4 the protein by This is expression in of a of the NF-E4 Acetylation of the NF-E4 the of the factor the that such as can individual transcription factor erythroid protein erythroid protein as of transcription acetylation of the of This of of of the in of by acetylation provides factors in of the studied protein are the factors are the transcription factors such as erythroid factor of acetylation of in protein in in in the of of a number of individual protein the factors in the regulation of complex such is the in which a of genes is in a regulated of transcription factors that the of expression have of is a that is β-globin expression the in the of is regulated by acetylation by that in of the protein the complex is transcription factor This protein the protein complex the transcription factor facilitates the of the γ-globin genes the in the in fetal erythroid the in the expression of NF-E4 in the human human fetal expression fetal genes expression of NF-E4 a in β-globin expression that NF-E4 is a of the acetylation of in NF-E4 in in the of the protein by in that a in functional that the of NF-E4 fetal in fetal in fetal in of of by a the expression in the the by by by in by of the by by of of of that by the that the of the by a the of the β-globin the the the the by as by the the one of which in of the in a the in a the the by the by the in in fetal a of in by in a by by protein by the by in in as NF-E4 the by of protein the the protein by Acetylation of the protein of protein in a of by of by protein as the in a of of the by in the of by of by of protein protein in by the as NF-E4 in NF-E4 in the the of the of NF-E4 in in functional the transcription factors factors are erythroid Acetylation of is role as that a NF-E4 We the of NF-E4 as a protein in the of the of by which is in by as the as the shown in acetylation of in the of of the of NF-E4, in the of NF-E4 in in a human in the of a shown in the NF-E4 NF-E4 directly the role of in the acetylation of NF-E4 in a the human expression a NF-E4 the a a that the a the in the of NF-E4 in the of of NF-E4 in role expression of in the that NF-E4 as a the in in of transcription factors is by a the factor the NF-E4 directly NF-E4 which the a protein the the of NF-E4 that a of of NF-E4 as NF-E4 the of that the the the in a expression the NF-E4 a the a NF-E4 the the that the in a of the NF-E4 We in the of expression of the NF-E4 the shown in NF-E4 that factors a complex in cells. in in of in protein by of the in NF-E4 in the in of NF-E4 protein by of the in in the expression NF-E4 the by NF-E4 protein in as the by protein in Acetylation in the in NF-E4 that are by of a in acetylation protein acetylation NF-E4 NF-E4 in NF-E4 the NF-E4 of protein expression This acetylation by of in the in the of acetylation of NF-E4 the that the acetylation of the NF-E4 protein by the is of NF-E4 by of the by is shown in the the of NF-E4 is shown in of the is shown the NF-E4 the by expression NF-E4 the by of the of the of of the of NF-E4 in a NF-E4 acetylation by in a NF-E4 protein in which the of the NF-E4 in the of by shown in as acetylation in the setting of the This the of NF-E4 the of the protein the of the NF-E4 acetylation in expression the NF-E4 a NF-E4 the shown in expression of the NF-E4 as a in the setting of the the protein acetylation as the of in acetylation the of in by Acetylation in of transcription factors are by acetylation the of NF-E4 NF-E4 the human the the in NF-E4 in the of the in of NF-E4 the in of NF-E4 NF-E4 a complex of complex by the acetylation of the by NF-E4 complex that by the acetylation of NF-E4 We a complex the of NF-E4 the of the the of shown in the of a of in of the a of the complex that acetylation of NF-E4 of NF-E4 NF-E4 in as a the the of NF-E4 in the of the of the Acetylation of the protein by complex is the the is a complex that is by NF-E4 by shown the of a number of transcription factors We the of acetylation NF-E4 protein by the of NF-E4 in the as a NF-E4 as a expression of shown be in the by shown in a in NF-E4 in the the of NF-E4 in that the of NF-E4 is acetylation of of NF-E4 the the of NF-E4 in the as of a are shown of in the by that of protein in the of in the by of NF-E4 is as a of the the of the the the of the of as in a is shown of is as a of the the of the the the of the of as the in in in the of the by the of NF-E4 NF-E4 is as of NF-E4 acetylation a expression the as a by of the NF-E4 by the the a are in the the NF-E4 are as the is of protein in the by the expression of is shown in the the of NF-E4 as of the the NF-E4 We of expression that in the of a in NF-E4 expression in the cells. the of the the of the in that acetylation of role in the of the NF-E4 protein in cells. that a role in the of of NF-E4 the of the the transcription factors the proteins, the of acetylation that protein are the by acetylation of protein acetylation of NF-E4 the of the protein NF-E4 in as in in NF-E4 in the of as a Acetylation of NF-E4 protein in the of the of in as by acetylation in the of by This that acetylation of the of the of of the of NF-E4 in a the the NF-E4 the of expression of the NF-E4 in a in the protein in a expression the of expression of the in the of expression the NF-E4 a in We of expression in NF-E4 in the the cells. in the in the cells. that is by in of NF-E4 that functional of of NF-E4 be by in the of the the in which expression of NF-E4 a as a a the the a This the the of the is shown in a in in the the in in the in the the of expression of the protein This that of the NF-E4 protein in the that acetylation of the protein role in NF-E4 a γ-globin the NF-E4 a human γ-globin the the a as the of the of in the of in the by of in the by the human γ-globin a the the in the of the of as the of in the of the in a the the of which in shown in a in This the of expression of NF-E4 are a of transcription factor acetylation of the complex is by acetylation of NF-E4 protein We that NF-E4 the is a of a of in in acetylation of NF-E4 in a in Acetylation of the protein by of the the that NF-E4 of NF-E4 as by that acetylation of NF-E4 a role in the of the factor protein the of as the by protein in in the of the of as the by of in the by of the the acetylation of NF-E4 in by of is shown the in have that NF-E4 a role in regulation of the human β-globin of the of expression are of the the fetal erythroid NF-E4 is a component of a complex that the We that the NF-E4 in the This a number of of the protein of protein that of NF-E4 is the of the NF-E4 the NF-E4 protein a number of that in the of the is We that directly the NF-E4 NF-E4 is of the erythroid transcription factors that the of which are by factors have directly in of the β-globin the fetal NF-E4 are by the that of the This a the of the of factors such as NF-E4 that are expression of factors of erythroid functional of acetylation of of the factors have of the component of the of complex is We of acetylation the of NF-E4, a that the of of acetylation of acetylation the factor the complex This in of the of the acetylation of NF-E4 of the protein a the is a of a of in of have in the role of such are be the of as protein of NF-E4 the complex the that NF-E4 a role in fetal regulation the of a number of transcription factors shown of acetylation of the of factors acetylation the the in the of NF-E4 that transcription shown have the complex This a mechanism the of a factor a complex of NF-E4 in the of acetylation a number of transcription of the the that by that acetylation of the of the that a mechanism NF-E4 acetylation of by the of in the complex NF-E4 be is that be by NF-E4 as a erythroid protein erythroid protein as of transcription acetylation of the of This of of of the in of by acetylation provides factors in of the studied protein are the factors are the transcription factors such as erythroid 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a of in by in a by by protein by the by in in as NF-E4 the by of protein the the protein by Acetylation of the protein of protein in a of by of by protein as the in a of of the by in the of by of by of protein protein in by the as NF-E4 in NF-E4 in the the of the in fetal in fetal in of of by a the expression in the the by by by in by of the by by of of of that by the that the of the by a the of the β-globin the the the the by as by the the one of which in of the in a the in a the the by the by the in in fetal a of in by in a by by protein by the by in in as NF-E4 the by of protein the the protein by Acetylation of the protein of protein in a of by of by protein as the in a of of the by in the of by of by of protein protein in by the as NF-E4 in NF-E4 in the the of the of NF-E4 in in functional the transcription factors factors are erythroid Acetylation of is role as that a NF-E4 We the of NF-E4 as a protein in the of the of by which is in by as the as the shown in acetylation of in 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