Disruption of human vigilin impairs chromosome condensation and segregation

Abstract

Appropriate packaging and condensation are critical for eukaryotic chromatin's accommodation and separation during cell division. Human vigilin, a multi-KH-domain nucleic acid-binding protein, is associated with alpha satellites of centromeres. DDP1, a vigilin's homolog, is implicated with chromatin condensation and segregation. The expression of vigilin was previously reported to elevate in highly proliferating tissues and increased in a subset of hepatocellular carcinoma patients. Other studies showed that vigilin interacts with CTCF, contributes to regulation of imprinted genes Igf2/H19, and colocalizes with HP1α on heterochromatic satellite 2 and β-satellite repeats. These studies indicate that human vigilin might be involved in chromatin remodeling and regular cell growth. To investigate the potential role of human vigilin in cell cycle, the correlations between vigilin and chromosomal condensation and segregation were studied. Depletion of human vigilin by RNA interference in HepG2 cells resulted in chromosome undercondensation and various chromosomal defects during mitotic phase, including chromosome misalignments, lagging chromosomes, and chromosome bridges. Aberrant polyploid nucleus in telophase was also observed. Unlike the abnormal staining pattern of chromosomes, the shape of spindle was normal. Furthermore, the chromatin showed a greater sensitivity to MNase digestion. Collectively, our findings show that human vigilin apparently participates in chromatin condensation and segregation.

Spatial Cross-Talk between Oxidative Stress and DNA Replication in Human Fibroblasts

“…After original identification as a plasma membrane protein that was estrogen-inducible and sensitive to cholesterol, this role was little investigated further. As a protein highly conserved from yeast to mammals that contains 14 KH domains involved in nucleotide binding, research instead concentrated on putative roles in chromatin silencing together with PRKDC/XRCC5,6 ,, and on translational control via mRNA interactions. − It is known to partition between the nucleus and the cytoplasm. Recently HDLBP has been shown to function as a receptor for a potential anticancer agent in plasma membrane lipid rafts and to interact with CCCTC-binding factor (CTCF) involved in CTCF-dependent regulation of the imprinted genes IGF2 and H19, and as a candidate tumor suppressor deleted at 2q37.3 in tumor cells generated from many tissue types with insertional mutagenesis screens .…”

“…After original identification as a plasma membrane protein that was estrogen-inducible and sensitive to cholesterol, this role was little investigated further. As a protein highly conserved from yeast to mammals that contains 14 KH domains involved in nucleotide binding, research instead concentrated on putative roles in chromatin silencing together with PRKDC/XRCC5,6 42,128,129 and on translational control via mRNA interactions. [130][131][132] It is known to partition between the nucleus and the cytoplasm.…”

A jack of all trades: the RNA‐binding protein vigilin

“…Deletion of vigilin in S. cerevisiae resulted in mutants with increased DNA content/ploidy 5,17 whereas knockdown of vigilin in Drosophila S2 and human liver cells led to defects in chromosome condensation manifesting in chromosome misalignment and lagging during division. [18][19][20] While these observations attribute a role for vigilin in chromatin organization, vigilin has also been observed to influence many stages of RNA metabolism, including mRNA transport, 21,22 translation, 2,23-25 degradation, 4,26 and formation of stress granules 27 and processing bodies (P-bodies). 28 Despite an abundance of research into the vigilin proteins since their identification 30 years ago, our understanding of their exact functions in the cell remains unclear.…”