Bromodomain Protein BRD4 Is Essential for Hair Cell Function and Survival

Abhiraami Kannan-Sundhari; Clemer Abad; Marie E Maloof; Nagi G Ayad; Juan I Young; Xue Zhong Liu; Katherina Walz

doi:10.3389/fcell.2020.576654

Bromodomain Protein BRD4 Is Essential for Hair Cell Function and Survival

Front Cell Dev Biol. 2020 Sep 8:8:576654. doi: 10.3389/fcell.2020.576654. eCollection 2020.

Authors

Abhiraami Kannan-Sundhari^{1

2}, Clemer Abad³, Marie E Maloof⁴, Nagi G Ayad⁴, Juan I Young^{2

3}, Xue Zhong Liu^{1

2

3}, Katherina Walz^{2

3}

Affiliations

¹ Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami, FL, United States.
² The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, FL, United States.
³ John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, United States.
⁴ The Miami Project to Cure Paralysis, Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, United States.

Abstract

Hair cells (HCs) play crucial roles in perceiving sound, acceleration, and fluid motion. The tonotopic architecture of the sensory epithelium recognizes mechanical stimuli and convert them into electrical signals. The expression and regulation of the genes in the inner ear is very important to keep the sensory organ functional. Our study is the first to investigate the role of the epigenetic reader Brd4 in the mouse inner ear. We demonstrate that HC specific deletion of Brd4 in vivo in the mouse inner ear is sufficient to cause profound hearing loss (HL), degeneration of stereocilia, nerve fibers and HC loss postnatally in mouse; suggesting an important role in hearing function and maintenance.

Keywords: Brd4; function; hair cell loss; hair cells; hearing loss; survival.