Acetylation of EKLF is essential for epigenetic modification and transcriptional activation of the beta-globin locus.

Molecular and Cellular Biology
Tanushri SenguptaJames J Bieker

Abstract

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 epigene...Continue Reading

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Citations

Mar 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Tanushri SenguptaJames J Bieker
Aug 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Miroslawa SiateckaLuanne L Peters
Jun 15, 2011·Proceedings of the National Academy of Sciences of the United States of America·Caroline MasJames G Omichinski
Mar 7, 2012·The Journal of Biological Chemistry·Yvette Y Yien, James J Bieker
Nov 10, 2009·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·George Fromm, Michael Bulger
Jun 6, 2009·Annual Review of Biochemistry·Aled Edwards
Oct 21, 2010·Physiological Reviews·Beth B McConnell, Vincent W Yang
Oct 12, 2012·PloS One·Aurelie D DesgardinJohn M Cunningham
May 27, 2011·Blood·Miroslawa Siatecka, James J Bieker
Sep 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Shefali SoniJames J Bieker
Jul 15, 2016·Journal of Biomedical Science·Jayu Jen, Yi-Ching Wang
Apr 28, 2018·Scientific Reports·Merlin Nithya GnanapragasamJames J Bieker
Jun 8, 2018·JACC. Basic to Translational Science·Nina M PollakKonstantinos Drosatos
Nov 15, 2020·International Journal of Molecular Sciences·Min Young KimYi Qiu

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