RESUMEN
Little is known about how combinations of histone marks are interpreted at the level of nucleosomes. The second PHD finger of human BPTF is known to specifically recognize histone H3 when methylated on lysine 4 (H3K4me2/3). Here, we examine how additional heterotypic modifications influence BPTF binding. Using peptide surrogates, three acetyllysine ligands are indentified for a PHD-adjacent bromodomain in BPTF via systematic screening and biophysical characterization. Although the bromodomain displays limited discrimination among the three possible acetyllysines at the peptide level, marked selectivity is observed for only one of these sites, H4K16ac, in combination with H3K4me3 at the mononucleosome level. In support, these two histone marks constitute a unique trans-histone modification pattern that unambiguously resides within a single nucleosomal unit in human cells, and this module colocalizes with these marks in the genome. Together, our data call attention to nucleosomal patterning of covalent marks in dictating critical chromatin associations.
Asunto(s)
Antígenos Nucleares/metabolismo , Histonas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Nucleosomas/metabolismo , Factores de Transcripción/metabolismo , Acetilación , Animales , Núcleo Celular/metabolismo , Cromatina/química , Cromatina/metabolismo , Código de Histonas , Histonas/química , Humanos , Modelos Moleculares , Nucleosomas/química , Péptidos/química , Péptidos/metabolismo , Procesamiento Proteico-Postraduccional , Estructura Terciaria de Proteína , XenopusRESUMEN
Purpose: The purpose of this study was to examine national trends and demographic associations with dental utilization among young children over 20 years (1996 to 2016). Methods: Data from the Medical Expenditure Panel Survey from 1996 to 2016 was used to estimate nationally representative rates of dental utilization among children. Results: From 1996 to 2016, the largest relative increases in dental utilization were seen among zero- to one-year-olds (odds ratio equals 6.20) and two- to three-year-olds (odds ratio equals 2.15), whereas older age groups had smaller relative increases (all odds ratios equal less than 1.5). However, in 2016, only 5.3 percent of zero- to one-year-olds and 31.0 percent of two- to three-year-olds visited a dentist. Conclusion: Despite large relative increases in dental utilization among zero- to three-year-olds, a vast majority of these children do not visit a dentist, suggesting that guidelines on establishing a dental home by age one are not adequately implemented.