Acetylation of EKLF is essential for epigenetic modification and transcriptional activation of the beta-globin locus.
Posttranslational modifications of transcription factors provide alternate protein interaction platforms that lead to varied downstream effects. We have investigated how the acetylation of EKLF plays a role in its ability to alter the beta-like globin locus chromatin structure and activate transcription of the adult beta-globin gene. By establishing an EKLF-null erythroid line whose closed beta-locus chromatin structure and silent beta-globin gene status can be rescued by retroviral infection of EKLF, we demonstrate the importance of EKLF acetylation at lysine 288 in the recruitment of CBP to the locus, modification of histone H3, occupancy by EKLF, opening of the chromatin structure, and transcription of adult beta-globin. We also find that EKLF helps to coordinate this process by the specific association of its zinc finger domain with the histone H3 amino terminus. Although EKLF interacts equally well with H3.1 and H3.3, we find that only H3.3 is enriched at the adult beta-globin promoter. These data emphasize the critical nature of lysine acetylation in transcription factor activity and enable us to propose a model of how modified EKLF integrates coactivators, chromatin remodelers, and nucleosomal components to alter epigenetic chromatin structure and stimulate transcription.
Sengupta
Tanushri
T
Mount Sinai School of Medicine, New York, NY 10029, USA.
Chen
Ken
K
Milot
Eric
E
Bieker
James J
JJ
D000107:Acetylation; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000378:metabolism; D044127:Epigenesis, Genetic; D041905:Erythroid Cells; D005914:Globins / Q000235:genetics*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D015533:Transcriptional Activation / Q000235:genetics*; D016335:Zinc Fingers
D002843:Chromatin; D006657:Histones; D051741:Kruppel-Like Transcription Factors; C080774:erythroid Kruppel-like factor; D005914:Globins; D004247:DNA; D008239:Lysine