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Approaches for the study of epigenetic modifications in the inner ear and related tissues.

ABSTRACT: DNA methylation and histone modifications such as methylation, acetylation, and phosphorylation, are two types of epigenetic modifications that alter gene expression. These additions to DNA regulatory elements or to the tails of histones can be inherited or can also occur de novo. Since epigenetic modifications can have significant effects on various processes at both the cellular and organismal level, there has been a rapid increase in research on this topic throughout all fields of biology in recent years. However, epigenetic research is relativity new for the inner ear field, likely due to the limited number of cells present and their quiescent nature. Here, we provide an overview of methods used to detect DNA methylation and histone modifications with a focus on those that have been validated for use with limited cell numbers and a discussion of the strengths and limitations for each. We also provide examples for how these methods have been used to investigate the epigenetic landscape in the inner ear and related tissues.

SUBMITTER: Walters BJ

PROVIDER: S-EPMC6456365 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Approaches for the study of epigenetic modifications in the inner ear and related tissues.

Walters Bradley J BJ Cox Brandon C BC

Hearing research 20190112

DNA methylation and histone modifications such as methylation, acetylation, and phosphorylation, are two types of epigenetic modifications that alter gene expression. These additions to DNA regulatory elements or to the tails of histones can be inherited or can also occur de novo. Since epigenetic modifications can have significant effects on various processes at both the cellular and organismal level, there has been a rapid increase in research on this topic throughout all fields of biology in ...[more]

PMID: 30679030

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Project description:Background: Like the brain, the human inner ear was long thought to be devoid of immune activity. Only the endolymphatic sac (ES) was known to be endowed with white blood cells that could process antigens and serve as an immunologic defense organ for the entire inner ear. Unexpectedly, the cochlear and vestibular organs, including the eighth cranial nerve, were recently shown to contain macrophages whose functions and implication in ear disease are somewhat undefined. Here, we review recent inner ear findings in man and extend the analyses to the vestibular nerve using super-resolution structured illumination microscopy (SR-SIM). Materials and Methods: Human ESs and cochleae were collected during surgery to treat patients with vestibular schwannoma and life-threatening petro-clival meningioma compressing the brainstem. The ESs and cochleae were placed in fixative, decalcified, and rapidly frozen and cryostat sectioned. Antibodies against ionized calcium-binding adaptor molecule 1-expressing cells (IBA1 cells), laminin β2 and type IV collagen TUJ1, cytokine fractalkine (CX3CL1), toll-like receptor 4 (TLR4), CD68, CD11b, CD4, CD8, the major histocompatibility complex type II (MHCII), and the microglial marker TEME119 were used. Results: IBA1-positive cells were present in the ESs, the cochlea, central and peripheral axons of the cochlear nerve, and the vestibular nerve trunk. IBA1 cells were found in the cochlear lateral wall, spiral limbus, and spiral ganglion. Notable variants of IBA1 cells adhered to neurons with "synapse-like" specializations and cytoplasmic projections. Slender IBA1 cells occasionally protracted into the basal lamina of the Schwann cells and had intimate contact with surrounding axons. Discussion: The human eighth nerve may be under the control of a well-developed macrophage cell system. A small number of CD4+ and CD8+ cells were found in the ES and occasionally in the cochlea, mostly located in the peripheral region of Rosenthal's canal. A neuro-immunologic axis may exist in the human inner ear that could play a role in the protection of the auditory nerve. The implication of the macrophage system during disease, surgical interventions, and cell-based transplantation should be further explored.

Dataset Information

Approaches for the study of epigenetic modifications in the inner ear and related tissues.

Publications

Approaches for the study of epigenetic modifications in the inner ear and related tissues.

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