The chromatin reader ZMYND8 regulates Igh enhancers to promote immunoglobulin class switch recombination

Class switch recombination (CSR) is a DNA recombination reaction that diversifies the effector component of antibody responses. CSR is initiated by activation-induced cytidine deaminase (AID), which targets transcriptionally active immunoglobulin heavy chain (Igh) switch donor and acceptor DNA. The 3' Igh super-enhancer, 3' regulatory region (3'RR), is essential for acceptor region transcription, but how this function is regulated is unknown. Here, we identify the chromatin reader ZMYND8 as an essential regulator of the 3'RR. In B cells, ZMYND8 binds promoters and super-enhancers, including the Igh enhancers. ZMYND8 controls the 3'RR activity by modulating the enhancer transcriptional status. In its absence, there is increased 3'RR polymerase loading and decreased acceptor region transcription and CSR. In addition to CSR, ZMYND8 deficiency impairs somatic hypermutation (SHM) of Igh, which is also dependent on the 3'RR. Thus, ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the activity of the 3' Igh super-enhancer

Supplementary Material for: Spontaneous Corneal Clearing After Descemet Membrane Rupture and Near-Total Detachment in Keratoglobus: A Case Report

Introduction: We present a case of patient with osteogenesis imperfecta (OI) and keratoglobus (KG) who had a near-total rupture of Descemet’s membrane followed by spontaneous corneal clearing. This case is unique in that it demonstrates the potentially excellent outcome of conservative treatment for Descemet’s rupture in patients with KG and illustrates the impressive migratory potential of healthy endothelial cells. Case Presentation: An 11-year-old girl with osteogenesis imperfecta (OI) and keratoglobus (KG) who had rupture and near-total detachment of Descemet’s membrane presented for evaluation. This was managed conservatively and resulted in eventual spontaneous clearing of the cornea. A similar process happened in the fellow eye some years later. Given the result of conservative management originally, the patient was once again treated conservatively with significant improvement in corneal edema and visual acuity. Conclusion: Given the size of the ruptures, this case highlights the dynamic nature of the corneal endothelium and provides an extreme example of the migratory potential of corneal endothelial cells