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-Structure paper
タイトル | Basic helix-loop-helix pioneer factors interact with the histone octamer to invade nucleosomes and generate nucleosome-depleted regions. |
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ジャーナル・号・ページ | Mol Cell, Vol. 83, Issue 8, Page 1251-11263.e6, Year 2023 |
掲載日 | 2023年4月20日 |
著者 | Benjamin T Donovan / Hengye Chen / Priit Eek / Zhiyuan Meng / Caroline Jipa / Song Tan / Lu Bai / Michael G Poirier / |
PubMed 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. |
リンク | Mol Cell / PubMed:36996811 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.2 Å |
構造データ | EMDB-25406, PDB-7ssa: |
由来 |
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キーワード | GENE REGULATION (遺伝子発現の調節) / Transcription factor (転写因子) / basic helix-loop-helix (塩基性ヘリックスループヘリックス) / complex |