Multiple enhancers located in a 1-Mb region upstream of POU3F4 promote expression during inner ear development and may be required for hearing

Naranjo, Silvia; Voesenek, Krysta; Calle‐Mustienes, Elisa de la; Robert‐Moreno, Alexandre; Kokotas, Haris; Grigoriadou, Maria; Economides, John R.; Camp, Guy Van; Hilgert, Nele; Moreno, Felipe; Alsina, Berta; Petersen, Michael B.; Kremer, Hannie; Gómez-Skármeta, José Luis

doi:10.1007/s00439-010-0864-x

Cited by 35 publications

(35 citation statements)

References 26 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, numerous cis-regulatory regions of animal genes have been shown to contain multiple enhancers with overlapping or very similar expression patterns (Jeong et al, 2006;Werner et al, 2007;Hong et al, 2008;McGaughey et al, 2008;Corbo et al, 2010;Frankel et al, 2010;Kalay and Wittkopp, 2010;L'Honore et al, 2010;Naranjo et al, 2010;Perry et al, 2010Perry et al, , 2011Franchini et al, 2011;Galindo et al, 2011;Ghiasvand et al, 2011;Lee et al, 2011;McBride et al, 2011;Watts et al, 2011;Pauls et al, 2012). Yet, the first observations of overlapping expression from different enhancers date back from the 1990s (Hoch et al, 1990;Kassis, 1990;Tolias and Kafatos, 1990).…”

Section: Genes Have Multiple Enhancers With Overlapping or Very Similmentioning

confidence: 99%

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Frankel

2012

Developmental Dynamics

View full text Add to dashboard Cite

Genomes contain the necessary information to ensure that genes are expressed in the right place, at the right time, and with the proper rate. Metazoan developmental genes often possess long stretches of DNA flanking their coding sequences and/or large introns which contain elements that influence gene expression. Most of these regulatory elements are relatively small and can be studied in isolation. For example, transcriptional enhancers, the elements that generate the expression pattern of a gene, have been traditionally studied with reporter constructs in transgenic animals. These studies have provided and will provide invaluable insights into enhancer evolution and function. However, this experimental approach has its limits; often, enhancer elements do not faithfully recapitulate native expression patterns. This fact suggests that additional information in cis-regulatory regions modulates the activity of enhancers and other regulatory elements. Indeed, recent studies have revealed novel functional aspects at the level of whole cis-regulatory regions. First, the discovery of ''shadow enhancers.'' Second, the ubiquitous interactions between cis-regulatory elements. Third, the notion that some cis-regulatory regions may not function in a modular manner. Last, the effect of chromatin conformation on cis-regulatory activity. In this article, I describe these recent findings and discuss open questions in the field.

show abstract

Section: Genes Have Multiple Enhancers With Overlapping or Very Similmentioning

confidence: 99%

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Frankel

2012

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…Distal enhancers can regulate their target genes from long distances, the most extreme case being the Shh gene’s enhancer at ∼1 Mb away, and are especially important in regulating critical developmental genes (3,4). Recent advances in sequencing technologies have revealed that cell-specific enhancers are often marked by P300 binding (a histone acetyltransferase and transcription coactivator) (5,6), as well as other epigenomic marks such as DNAse hypersensitivity (DHS), H3K4me1, H3K27ac and so forth.…”

Section: Introductionmentioning

confidence: 99%

Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers

Malin¹,

Aniba²,

Hannenhalli³

2013

Nucleic Acids Research

View full text Add to dashboard Cite

Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using ∼100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity. We found widespread correlated activity between enhancers, which decreases with increasing inter-enhancer genomic distance. We found that correlated enhancers tend to share common transcription factor (TF) binding motifs, and several chromatin modification enzymes preferentially interact with these TFs. Presence of shared motifs in enhancer pairs can predict correlated activity with 73% accuracy. Also, genes near correlated enhancers exhibit correlated expression and share common function. Correlated enhancers tend to be spatially proximal. Interestingly, weak enhancers tend to correlate with significantly greater numbers of other enhancers relative to strong enhancers. Furthermore, strong/weak enhancers preferentially correlate with strong/weak enhancers, respectively. We constructed enhancer networks based on shared motif and correlated activity and show significant functional enrichment in their putative target gene clusters. Overall, our analyses show extensive correlated activity among enhancers and reveal clusters of enhancers whose activities are coordinately regulated by multiple potential mechanisms involving shared TF binding, chromatin modifying enzymes and 3D chromatin structure, which ultimately co-regulate functionally linked genes.

show abstract

“…3, 18–20 However, it is difficult to detect such large genomic alterations using conventional PCR-based DNA sequencing. Anger et al have reported normal genetic sequencing results in a DFNX2 case with chromosomal rearrangements in the vicinity of POU3F4 , suggesting a failure of Sanger sequencing to identify mutations because of genetic causes.…”

Section: Discussionmentioning

confidence: 99%

De Novo Mutation in X-Linked Hearing Loss–Associated POU3F4 in a Sporadic Case of Congenital Hearing Loss

Moteki

Shearer

Izumi

et al. 2015

Ann Otol Rhinol Laryngol

View full text Add to dashboard Cite

Objective In this report, we present a male patient with no family history of hearing loss, in whom we identified a novel de novo mutation in the POU3F4 gene. Methods One hundred ninety-four (194) Japanese subjects from unrelated and families were enrolled in this study. We used targeted genomic enrichment and massively parallel sequencing of all known non-syndromic hearing loss genes for identifying the genetic causes of hearing loss. Results A novel de novo frameshift mutation of POU3F4, to c.727_728insA (p.N244KfsX26) was identified. The patient was a 7-year-old male with congenital progressive hearing loss and inner ear deformity. Although the patient had received a cochlear implant, auditory skills were still limited. The patient also exhibited developmental delays similar to those previously associated with POU3F4 mutation. Conclusion This is the first report of a mutation in POU3F4 causing hearing loss in a Japanese patient without a family history of hearing loss. This study underscores the importance of comprehensive genetic testing of patients with hearing loss for providing accurate prognostic information and guiding the optimal management of patient rehabilitation.

show abstract

Multiple enhancers located in a 1-Mb region upstream of POU3F4 promote expression during inner ear development and may be required for hearing

Cited by 35 publications

References 26 publications

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers

De Novo Mutation in X-Linked Hearing Loss–Associated POU3F4 in a Sporadic Case of Congenital Hearing Loss

Contact Info

Product

Resources

About