Perspectives on Codebook: sequence specificity of uncharacterized human transcription factors.

We describe an effort ("Codebook") to determine the sequence specificity of 332 putative and largely uncharacterized human transcription factors (TFs), as well as 61 control TFs. Nearly 5,000 independent experiments across multiple and assays produced motifs for just over half of the putative TFs analyzed (177, or 53%), of which most are unique to a single TF. The data highlight the extensive contribution of transposable elements to TF evolution, both in and , and identify tens of thousands of conserved, base-level binding sites in the human genome.

Extensive binding of uncharacterized human transcription factors to genomic dark matter.

Most of the human genome is thought to be non-functional, and includes large segments often referred to as "dark matter" DNA. The genome also encodes hundreds of putative and poorly characterized transcription factors (TFs). We determined genomic binding locations of 166 uncharacterized human TFs in living cells.

Reconstruction of full-length LINE-1 progenitors from ancestral genomes.

Sequences derived from the Long INterspersed Element-1 (L1) family of retrotransposons occupy at least 17% of the human genome, with 67 distinct subfamilies representing successive waves of expansion and extinction in mammalian lineages. L1s contribute extensively to gene regulation, but their molecular history is difficult to trace, because most are present only as truncated and highly mutated fossils. Consequently, L1 entries in current databases of repeat sequences are composed mainly of short diagnostic subsequences, rather than full functional progenitor sequences for each subfamily.

Diverse Eukaryotic CGG-Binding Proteins Produced by Independent Domestications of hAT Transposons.

The human transcription factor (TF) CGGBP1 (CGG-binding protein) is conserved only in amniotes and is believed to derive from the zf-BED and Hermes transposase DNA-binding domains (DBDs) of a hAT DNA transposon. Here, we show that sequence-specific DNA-binding proteins with this bipartite domain structure have resulted from dozens of independent hAT domestications in different eukaryotic lineages. CGGBPs display a wide range of sequence specificity, usually including preferences for CGG or CGC trinucleotides, whereas some bind AT-rich motifs.

DNA Methylation of the Oxytocin Receptor Across Neurodevelopmental Disorders.

Many neurodevelopmental disorders (NDDs) share common learning and behavioural impairments, as well as features such as dysregulation of the oxytocin hormone. Here, we examined DNA methylation (DNAm) in the 1st intron of the oxytocin receptor gene, OXTR, in patients with autism spectrum (ASD), attention deficit and hyperactivity (ADHD) and obsessive compulsive (OCD) disorders. DNAm of OXTR was assessed for cohorts of ASD (blood), ADHD (saliva), OCD (saliva), which uncovered sex-specific DNAm differences compared to neurotypical, tissue-matched controls.