Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, United States. Electronic address: https://twitter.com/@pra_sidh.
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, United States.
Curr Opin Struct Biol. 2023 Oct;82:102694. doi: 10.1016/j.sbi.2023.102694. Epub 2023 Aug 30.
Centromeres are chromosomal regions that provide the foundation for microtubule attachment during chromosome segregation. Centromeres are epigenetically defined by nucleosomes containing the histone H3 variant centromere protein A (CENP-A) and, in many organisms, are surrounded by transcriptionally repressed pericentromeric chromatin marked by trimethylation of histone H3 lysine 9 (H3K9me3). Pericentromeric regions facilitate sister chromatid cohesion during mitosis, thereby supporting centromere function. Heterochromatin has a known propensity to spread into adjacent euchromatic domains unless it is properly bounded. Heterochromatin spreading into the centromere can disrupt kinetochore function, perturbing chromosome segregation and genome stability. In the fission yeast Schizosaccharomyces pombe, tRNA genes provide barriers to heterochromatin spread at the centromere, the absence of which results in abnormal meiotic chromosome segregation. How heterochromatin-centromere boundaries are established in humans is not understood. We propose models for stable epigenetic inheritance of centromeric domains in humans and discuss advances that will enable the discovery of novel regulators of this process.
着丝粒是染色体区域，为染色体分离过程中微管附着提供基础。着丝粒通过含有组蛋白 H3 变体着丝粒蛋白 A（CENP-A）的核小体在表观上定义，并且在许多生物体中，被转录抑制的着丝粒周围染色质包围，其特征是组蛋白 H3 赖氨酸 9（H3K9me3）的三甲基化。着丝粒周围区域在有丝分裂过程中促进姐妹染色单体的黏合，从而支持着丝粒功能。异染色质有向相邻常染色质区域扩散的已知趋势，除非它被适当限制。异染色质向着丝粒的扩散会破坏动粒功能，扰乱染色体分离和基因组稳定性。在裂殖酵母 Schizosaccharomyces pombe 中，tRNA 基因为着丝粒处异染色质的扩散提供了障碍，缺失这些基因会导致异常的减数分裂染色体分离。在人类中，异染色质-着丝粒边界是如何建立的尚不清楚。我们提出了人类着丝粒区域稳定的表观遗传遗传模型，并讨论了将有助于发现该过程新调节因子的进展。
