Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA; Abramson Family Cancer Research Center, Perelman School of Medicine at the University of Pennsylvania, Pennsylvania, USA.
Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA; Abramson Family Cancer Research Center, Perelman School of Medicine at the University of Pennsylvania, Pennsylvania, USA; Graduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine at the University of Pennsylvania, Pennsylvania, USA.
J Biol Chem. 2024 Sep;300(9):107604. doi: 10.1016/j.jbc.2024.107604. Epub 2024 Jul 24.
The HIRA histone chaperone complex is comprised of four protein subunits: HIRA, UBN1, CABIN1, and transiently associated ASF1a. All four subunits have been demonstrated to play a role in the deposition of the histone variant H3.3 onto areas of actively transcribed euchromatin in cells. The mechanism by which these subunits function together to drive histone deposition has remained poorly understood. Here we present biochemical and biophysical data supporting a model whereby ASF1a delivers histone H3.3/H4 dimers to the HIRA complex, H3.3/H4 tetramerization drives the association of two HIRA/UBN1 complexes, and the affinity of the histones for DNA drives release of ASF1a and subsequent histone deposition. These findings have implications for understanding how other histone chaperone complexes may mediate histone deposition.
HIRA 组蛋白伴侣复合物由四个蛋白质亚基组成：HIRA、UBN1、CABIN1 和瞬时相关的 ASF1a。所有四个亚基都已被证明在将组蛋白变体 H3.3 沉积到细胞中活跃转录的常染色质区域中发挥作用。这些亚基共同发挥作用以驱动组蛋白沉积的机制仍然知之甚少。在这里，我们提供生化和生物物理数据支持这样一种模型，即 ASF1a 将组蛋白 H3.3/H4 二聚体递送给 HIRA 复合物，H3.3/H4 四聚体化驱动两个 HIRA/UBN1 复合物的缔合，以及组蛋白与 DNA 的亲和力驱动 ASF1a 的释放和随后的组蛋白沉积。这些发现对于理解其他组蛋白伴侣复合物如何可能介导组蛋白沉积具有重要意义。
