Role of the Histone Amino Termini in Facilitated Binding of a Transcription Factor, GAL4-AH, to Nucleosome Cores

Abstract

Facilitated, "cooperative" binding of GAL4-AH to nucleosomal DNA occurred in response to inhibition from the core histone amino termini. The binding of GAL4-AH (which contains the DNA-binding and dimerization domains of GAL4) to nucleosome cores containing multiple binding sites initiated at the end of a nucleosome core and proceeded in a cooperative manner until all sites were occupied. However, following tryptic removal of the core histone amino termini, GAL4-AH binding appeared to be noncooperative, similar to binding naked DNA. Binding of GAL4-AH to nucleosomes bearing a single GAL4 site at different positions indicated that inhibition of GAL4 binding was largely mediated by the histone amino termini and primarily occurred at sites well within the core and not near the end. When the histone amino termini were intact, binding of GAL4-AH to sites near the center of a nucleosome core was greatly enhanced by the presence of additional GAL4 dimers bound to more-accessible positions. These data illustrate that the binding of a factor to more-accessible sites, near the end of a nucleosome, allows facilitated binding of additional factors to the center of the nucleosome, thereby overcoming repression from the core histone amino termini. This mechanism may contribute to the binding of multiple factors to complex promoter and enhancer elements in cellular chromatin.

DNA Sequence-Dependent Contributions of Core Histone Tails to Nucleosome Stability: Differential Effects of Acetylation and Proteolytic Tail Removal

“…Both removal and acetylation of the tails are thought to “loosen” the histone−DNA contacts due to the removal of positive charge in the vicinity of nucleosomal DNA. This is in line with studies in which either acetylation or removal of the tail domains has been coupled to increased transcription factor access ( − ).…”

A test of the pioneer factor hypothesis using ectopic liver gene activation

“…Although we found clear instances of sites independently pioneered by either FOXA1 or HNF4A, not all sites containing multiple motifs were pioneered in K562 cells, which comports with studies showing that the sequence context in which motifs occur also plays an important role in determining whether sites will be pioneered or not. GAL4’s ability to bind nucleosomal DNA templates depends both on the number of copies of its motif ( Taylor et al, 1991 ) and the positioning of the motif in the nucleosome ( Vettese-Dadey et al, 1994 ). Precise nucleosome positioning also dictates TP53 and OCT4 pioneering behavior ( Yu and Buck, 2019 ; Huertas et al, 2020 ).…”

Chromatin Hyperacetylation Abrogates Vitamin D-Mediated Transcriptional Upregulation of the Tissue-Specific Osteocalcin Gene in Vivo

“…It is generally assumed that binding of transcription factors to nucleosomal DNA is enhanced by acetylation. This assumption is based on the demonstration that hyperacetylation induces subtle alterations in nucleosomal structure which may increase the accessibility to transcription factors (13)(14)(15)(16). Nevertheless, Hager and colleagues reported that butyrate treatment inhibited glucocorticoid hormone-dependent formation of a nuclease hypersensitive site and blocked transcriptional induction of the mouse mammary tumor virus (MMTV) LTR (69).…”

“…The role of nucleosomes in regulating transcriptional activity is supported by histone acetylation experiments. Hyperacetylation of core histones has been shown to enhance binding of some transcription factors to nucleosomes (13)(14)(15)(16). One possible mechanism is that the histone basic N-terminal domains interact with nucleosomal DNA and prevent binding of transcription factors.…”