Chromatin activity identifies differential gene regulation across human ancestries.

Background: Current evidence suggests that cis-regulatory elements controlling gene expression may be the predominant target of natural selection in humans and other species. Detecting selection acting on these elements is critical to understanding evolution but remains challenging because we do not know which mutations will affect gene regulation.

Results: To address this, we devise an approach to search for lineage-specific selection on three critical steps in transcriptional regulation: chromatin activity, transcription factor binding, and chromosomal looping.

A subset of SMN complex members have a specific role in tissue regeneration via ERBB pathway-mediated proliferation.

Spinal muscular atrophy (SMA) is the most common genetic disease in children. SMA is generally caused by mutations in the gene . The survival of motor neurons (SMN) complex consists of SMN1, Gemins (2-8), and Strap/Unrip.

Fine-mapping -regulatory variants in diverse human populations.

Unlabelled: Genome-wide association studies (GWAS) are a powerful approach for connecting genotype to phenotype. Most GWAS hits are located in cis-regulatory regions, but the underlying causal variants and their molecular mechanisms remain unknown. To better understand human -regulatory variation, we mapped quantitative trait loci for chromatin accessibility (caQTLs)-a key step in cis-regulation-in 1000 individuals from 10 diverse populations.

Guided genetic screen to identify genes essential in the regeneration of hair cells and other tissues.

Regenerative medicine holds great promise for both degenerative diseases and traumatic tissue injury which represent significant challenges to the health care system. Hearing loss, which affects hundreds of millions of people worldwide, is caused primarily by a permanent loss of the mechanosensory receptors of the inner ear known as hair cells. This failure to regenerate hair cells after loss is limited to mammals, while all other non-mammalian vertebrates tested were able to completely regenerate these mechanosensory receptors after injury.

Loss of Mgat5a-mediated -glycosylation stimulates regeneration in zebrafish.

Background: We are using genetics to identify genes specifically involved in hearing regeneration. In a large-scale genetic screening, we identified , a gene in the -glycosylation biosynthesis pathway whose activity negatively impacts hair cell regeneration.

Methods: We used a combination of mutant analysis in zebrafish and a hair cell regeneration assay to phenotype the loss of Mgat5a activity in zebrafish.

Spatial distribution of predicted transcription factor binding sites in Drosophila ChIP peaks.

In the development of the Drosophila embryo, gene expression is directed by the sequence-specific interactions of a large network of protein transcription factors (TFs) and DNA cis-regulatory binding sites. Once the identity of the typically 8-10bp binding sites for any given TF has been determined by one of several experimental procedures, the sequences can be represented in a position weight matrix (PWM) and used to predict the location of additional TF binding sites elsewhere in the genome. Often, alignments of large (>200bp) genomic fragments that have been experimentally determined to bind the TF of interest in Chromatin Immunoprecipitation (ChIP) studies are trimmed under the assumption that the majority of the binding sites are located near the center of all the aligned fragments.