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Posttranslational mechanisms controlling centromere function and assembly.

ABSTRACT: Accurate chromosome segregation is critical to ensure the faithful inheritance of the genome during cell division. Human chromosomes distinguish the location of the centromere from general chromatin by the selective assembly of CENP-A containing nucleosomes at the active centromere. The location of centromeres in most higher eukaryotes is determined epigenetically, independent of DNA sequence. CENP-A containing centromeric chromatin provides the foundation for assembly of the kinetochore that mediates chromosome attachment to the microtubule spindle and controls cell cycle progression in mitosis. Here we review recent work demonstrating the role of posttranslational modifications on centromere function and CENP-A inheritance via the direct modification of the CENP-A nucleosome and pre-nucleosomal complexes, the modification of the CENP-A deposition machinery and the modification of histones within existing centromeres.

SUBMITTER: Srivastava S

PROVIDER: S-EPMC6004306 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Posttranslational mechanisms controlling centromere function and assembly.

Srivastava Shashank S Zasadzińska Ewelina E Foltz Daniel R DR

Current opinion in cell biology 20180402

Accurate chromosome segregation is critical to ensure the faithful inheritance of the genome during cell division. Human chromosomes distinguish the location of the centromere from general chromatin by the selective assembly of CENP-A containing nucleosomes at the active centromere. The location of centromeres in most higher eukaryotes is determined epigenetically, independent of DNA sequence. CENP-A containing centromeric chromatin provides the foundation for assembly of the kinetochore that me ...[more]

PMID: 29621654

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Project description:The brain serotonin (5-hydroxytryptamine; 5-HT) system has been extensively studied for its role in normal physiology and behavior, as well as, neuropsychiatric disorders. The broad influence of 5-HT on brain function, is in part due to the vast connectivity pattern of 5-HT-producing neurons throughout the CNS. 5-HT neurons are born and terminally specified midway through embryogenesis, then enter a protracted period of maturation, where they functionally integrate into CNS circuitry and then are maintained throughout life. The transcriptional regulatory networks controlling progenitor cell generation and terminal specification of 5-HT neurons are relatively well-understood, yet the factors controlling 5-HT neuron maturation are only recently coming to light. In this review, we first provide an update on the regulatory network controlling 5-HT neuron development, then delve deeper into the properties and regulatory strategies governing 5-HT neuron maturation. In particular, we discuss the role of the 5-HT neuron terminal selector transcription factor (TF) Pet-1 as a key regulator of 5-HT neuron maturation. Pet-1 was originally shown to positively regulate genes needed for 5-HT synthesis, reuptake and vesicular transport, hence 5-HT neuron-type transmitter identity. It has now been shown to regulate, both positively and negatively, many other categories of genes in 5-HT neurons including ion channels, GPCRs, transporters, neuropeptides, and other transcription factors. Its function as a terminal selector results in the maturation of 5-HT neuron excitability, firing characteristics, and synaptic modulation by several neurotransmitters. Furthermore, there is a temporal requirement for Pet-1 in the control of postmitotic gene expression trajectories thus indicating a direct role in 5-HT neuron maturation. Proper regulation of the maturation of cellular identity is critical for normal neuronal functioning and perturbations in the gene regulatory networks controlling these processes may result in long-lasting changes in brain function in adulthood. Further study of 5-HT neuron gene regulatory networks is likely to provide additional insight into how neurons acquire their mature identities and how terminal selector-type TFs function in postmitotic vertebrate neurons.

Dataset Information

Posttranslational mechanisms controlling centromere function and assembly.

Publications

Posttranslational mechanisms controlling centromere function and assembly.

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