National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35 GM127034
米国
Estonian Research Council
PUTJD906
Estonia
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01 GM121858
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01 GM131626
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35 GM139564
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35 GM139654
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
T32 GM086252
米国
National Science Foundation (NSF, United States)
1715321
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
U24GM129547
米国
引用
ジャーナル: Mol Cell / 年: 2023 タイトル: Basic helix-loop-helix pioneer factors interact with the histone octamer to invade nucleosomes and generate nucleosome-depleted regions. 著者: Benjamin T Donovan / Hengye Chen / Priit Eek / Zhiyuan Meng / Caroline Jipa / Song Tan / Lu Bai / Michael G Poirier / 要旨: Nucleosomes drastically limit transcription factor (TF) occupancy, while pioneer transcription factors (PFs) somehow circumvent this nucleosome barrier. In this study, we compare nucleosome binding ...Nucleosomes drastically limit transcription factor (TF) occupancy, while pioneer transcription factors (PFs) somehow circumvent this nucleosome barrier. In this study, we compare nucleosome binding of two conserved S. cerevisiae basic helix-loop-helix (bHLH) TFs, Cbf1 and Pho4. A cryo-EM structure of Cbf1 in complex with the nucleosome reveals that the Cbf1 HLH region can electrostatically interact with exposed histone residues within a partially unwrapped nucleosome. Single-molecule fluorescence studies show that the Cbf1 HLH region facilitates efficient nucleosome invasion by slowing its dissociation rate relative to DNA through interactions with histones, whereas the Pho4 HLH region does not. In vivo studies show that this enhanced binding provided by the Cbf1 HLH region enables nucleosome invasion and ensuing repositioning. These structural, single-molecule, and in vivo studies reveal the mechanistic basis of dissociation rate compensation by PFs and how this translates to facilitating chromatin opening inside cells.