TY - JOUR
T1 - MicroRNAs and epigenetic regulation in the mammalian inner ear
T2 - Implications for deafness
AU - Friedman, Lilach M.
AU - Avraham, Karen B.
N1 - Funding Information:
Research done in the Avraham Laboratory was funded by NIH R01 DC005641, the Israel Science Foundation 1486/07, and the European Commission FP6 Integrated Projects EuroHear LSHG-CT-20054-512063 and Eumodic 037188. We thank Amiel Dror for drawing the figures and for the data in Fig. .
PY - 2009/10/1
Y1 - 2009/10/1
N2 - Sensorineural hearing loss is the most common sensory disorder in humans and derives, in most cases, from inner-ear defects or degeneration of the cochlear sensory neuroepithelial hair cells. Genetic factors make a significant contribution to hearing impairment. While mutations in 51 genes have been associated with hereditary sensorineural nonsyndromic hearing loss (NSHL) in humans, the responsible mutations in many other chromosomal loci linked with NSHL have not been identified yet. Recently, mutations in a noncoding microRNA (miRNA) gene, MIR96, which is expressed specifically in the inner-ear hair cells, were linked with progressive hearing loss in humans and mice. Furthermore, additional miRNAs were found to have essential roles in the development and survival of inner-ear hair cells. Epigenetic mechanisms, in particular, DNA methylation and histone modifications, have also been implicated in human deafness, suggesting that several layers of noncoding genes that have never been studied systematically in the inner-ear sensory epithelia are required for normal hearing. This review aims to summarize the current knowledge about the roles of miRNAs and epigenetic regulatory mechanisms in the development, survival, and function of the inner ear, specifically in the sensory epithelia, tectorial membrane, and innervation, and their contribution to hearing.
AB - Sensorineural hearing loss is the most common sensory disorder in humans and derives, in most cases, from inner-ear defects or degeneration of the cochlear sensory neuroepithelial hair cells. Genetic factors make a significant contribution to hearing impairment. While mutations in 51 genes have been associated with hereditary sensorineural nonsyndromic hearing loss (NSHL) in humans, the responsible mutations in many other chromosomal loci linked with NSHL have not been identified yet. Recently, mutations in a noncoding microRNA (miRNA) gene, MIR96, which is expressed specifically in the inner-ear hair cells, were linked with progressive hearing loss in humans and mice. Furthermore, additional miRNAs were found to have essential roles in the development and survival of inner-ear hair cells. Epigenetic mechanisms, in particular, DNA methylation and histone modifications, have also been implicated in human deafness, suggesting that several layers of noncoding genes that have never been studied systematically in the inner-ear sensory epithelia are required for normal hearing. This review aims to summarize the current knowledge about the roles of miRNAs and epigenetic regulatory mechanisms in the development, survival, and function of the inner ear, specifically in the sensory epithelia, tectorial membrane, and innervation, and their contribution to hearing.
UR - http://www.scopus.com/inward/record.url?scp=72849147946&partnerID=8YFLogxK
U2 - 10.1007/s00335-009-9230-5
DO - 10.1007/s00335-009-9230-5
M3 - Review article
C2 - 19876605
AN - SCOPUS:72849147946
SN - 0938-8990
VL - 20
SP - 581
EP - 603
JO - Mammalian Genome
JF - Mammalian Genome
IS - 9-10
ER -