Chromatin information content landscapes inform transcription factor and DNA interactions

Abstract

Interactions between transcription factors and chromatin are fundamental to genome organization and regulation and, ultimately, cell state. Here, we use information theory to measure signatures of organized chromatin resulting from transcription factor-chromatin interactions encoded in the patterns of the accessible genome, which we term chromatin information enrichment (CIE). We calculate CIE for hundreds of transcription factor motifs across human samples and identify two classes: low and high CIE. The 10–20% of common and tissue-specific high CIE transcription factor motifs, associate with higher protein–DNA residence time, including different binding site subclasses of the same transcription factor, increased nucleosome phasing, specific protein domains, and the genetic control of both chromatin accessibility and gene expression. These results show that variations in the information encoded in chromatin architecture reflect functional biological variation, with implications for cell state dynamics and memory.

Single-cell gene expression and chromatin accessibility profiling of human pancreatic islets at basal and stimulatory conditions nominates mechanisms of type 1 diabetes genetic risk

“… A ) Chromatin information enrichment calculation overview (adapted from ( 13 )). B ) V-plots showing aggregate ATAC-seq fragment midpoints distribution around predicted bound sites for three TFs (top facets) and their associated chromatin information enrichment (bottom facets) in beta cells and immune cells.…”

“…To characterize the epigenomic landscape of the different pancreatic cell types, we used the BMO tool ( 13 ) to predict bound transcription factor (TF) sites using a non-redundant collection of 540 motifs and calculated their chromatin information patterns. The observed chromatin information patterns reflect the impact of specific TFs in organizing local chromatin architecture and establishing cell identity ( 13 ) ( Figure 3A-B ). We identified common and cell-type-specific TFs driving the epigenomic landscape for each cell type ( Figure 3C) .…”

Pseudogenes and Liquid Phase Separation in Epigenetic Expression

“…Transcription factors are proteins that can bind to DNA sequences to regulate the rate of mRNA transcription process (34). To achieve transcription precision, the transcriptional factors activate LLPS to concentrate the super-enhancers, enrich the transcriptional factors, and bind the RNA polymerase II.…”

Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases

“…The ChIP-seq data for whole-genome histone modification profiles are also helpful in the search for ASB events on a genome-wide scale; these profiles characterize the energy landscape of chromatin, whereto the TF binding with regulatory regions considerably contributes [ 167 , 168 , 169 , 170 ]. In particular, this approach was implemented when searching for ASB events in K562, MCF-7, and HCT-116 human cell lines by analyzing the ENCODE ChIP-Seq data for histone epigenetic modifications (H3K27ac, H3K4me1, H3K4me2, H3K4me3, and H3K27me3) and 456 different chromatin-associated proteins, mainly transcriptional factors [ 171 ].…”