O‐GlcNAc Transferase and O‐GlcNAcase Interact with Mi2β at the Aγ‐Globin Promoter

• DOI: 10.1096/fasebj.30.1_supplement.803.3
• Publication Date: 2023-11-26T16:48:44Z
• Authors: Zhen Zhang; Flávia C. Costa; Ee Phie Tan; Nathan Bushue; Catherine E. Cost...; Mark E. McComb; Stephen A. Whelan; Kenneth R. Peterson; Chad Slawson

Sickle Cell Disease (SCD), caused by a point mutation in the adult β‐globin gene, leads to chronic damage multiple organs and stroke, as well cardiovascular abnormalities dysfunction. However, SCD patients are phenotypically normal if they carry compensatory mutations that result continued expression of fetal γ‐globin. Thus, logical clinical goal for treatment is up‐regulate γ‐globin synthesis. One mode silencing occurs at GATA binding sites located −566 or −567 relative A G transcription start site, respectively, mediated through DNA moiety GATA‐1 (GATA Binding Protein 1) its recruitment co‐repressor partners, FOG‐1 (Friend GATA‐1) Mi2β (CHD4, Chromodomain Helicase 4). Post‐translational modification factors can regulate their activity. such O‐GlcNAcylation, which attachment single N‐acetyl‐glucosamine serine threonine residues on nuclear, cytoplasmic mitochondrial proteins. O‐GlcNAc added proteins transferase (OGT) removed O‐GlcNAcase (OGA). Here, using ChIP (Chromatin Immunoprecipitation) assays, we demonstrate both OGT OGA interact with promoter when repressed wild‐type murine CID (Chemical Inducer Dimerization)‐dependent human β‐YAC (β‐globin locus yeast artificial chromosome) bone marrow cells (BMCs). In addition, recruited silencer site mouse embryonic day E18 liver repressed. Furthermore, FOG‐1, O‐GlcNAcylated co‐immunoprecipitation experiments. order confirm mapped one S85 mass spectrometry. Our data suggested GATA‐1/FOG‐1/Mi2β repressor complex activity promoter. Support Funding Information Research reported this publication was supported an Institutional Development Award (IDeA) from National Institute General Medical Sciences (NIGMS) Institutes Health under grant P20 GM12345, Diabetes Digestive Kidney Diseases R01 DK100595 C. Slawson K. Peterson, Heart, Lung, Blood contract HHSN268201000031C NIGMS P41 GM104603 E. Costello.