scholarly journals HP1 Proteins Are Essential for a Dynamic Nuclear Response That Rescues the Function of Perturbed Heterochromatin in Primary Human Cells

2006 ◽  
Vol 27 (3) ◽  
pp. 949-962 ◽  
Author(s):  
Rugang Zhang ◽  
Song-tao Liu ◽  
Wei Chen ◽  
Michael Bonner ◽  
John Pehrson ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Nucleotide Sequence ◽  
Small Molecules ◽  
Histone Modifications ◽  
Human Cells ◽  
Pericentromeric Heterochromatin ◽  
Dna Nucleotide Sequence ◽  
Nuclear Response ◽  
Hp1 Proteins ◽  
Primary Human Cells

ABSTRACT Cellular information is encoded genetically in the DNA nucleotide sequence and epigenetically by the “histone code,” DNA methylation, and higher-order packaging of DNA into chromatin. Cells possess intricate mechanisms to sense and repair damage to DNA and the genetic code. However, nothing is known of the mechanisms, if any, that repair and/or compensate for damage to epigenetically encoded information, predicted to result from perturbation of DNA and histone modifications or other changes in chromatin structure. Here we show that primary human cells respond to a variety of small molecules that perturb DNA and histone modifications by recruiting HP1 proteins to sites of altered pericentromeric heterochromatin. This response is essential to maintain the HP1-binding kinetochore protein hMis12 at kinetochores and to suppress catastrophic mitotic defects. Recruitment of HP1 proteins to pericentromeres depends on histone H3.3 variant deposition, mediated by the HIRA histone chaperone. These data indicate that defects in pericentromeric epigenetic heterochromatin modifications initiate a dynamic HP1-dependent response that rescues pericentromeric heterochromatin function and is essential for viable progression through mitosis.

scholarly journals Immortality, but not oncogenic transformation, of primary human cells leads to epigenetic reprogramming of DNA methylation and gene expression

2013 ◽  
Vol 42 (6) ◽  
pp. 3529-3541 ◽  
Author(s):  
Katrina Gordon ◽  
Thomas Clouaire ◽  
Xun X. Bao ◽  
Sadie E. Kemp ◽  
Maria Xenophontos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Human Cells ◽  
Epigenetic Reprogramming ◽  
Oncogenic Transformation ◽  
Primary Human Cells

scholarly journals DNA methylation in the Alu sequences of diploid and haploid primary human cells.

1993 ◽  
Vol 12 (3) ◽  
pp. 1141-1151 ◽  
Author(s):  
S. Kochanek ◽  
D. Renz ◽  
W. Doerfler
Keyword(s):  
Dna Methylation ◽  
Human Cells ◽  
Alu Sequences ◽  
Primary Human Cells

Effect of small molecules on cell reprogramming

2017 ◽  
Vol 13 (2) ◽  
pp. 277-313 ◽  
Author(s):  
M. Baranek ◽  
A. Belter ◽  
M. Z. Naskręt-Barciszewska ◽  
M. Stobiecki ◽  
W. T. Markiewicz ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Small Molecules ◽  
Chromatin Remodeling ◽  
Histone Modifications ◽  
Cell Reprogramming ◽  
Epigenetic Changes

Small molecules cause pluripotency induction through epigenetic changes such as DNA methylation, histone modifications, RNA noncoding and chromatin remodeling.

scholarly journals Neuroblastoma and the epigenome

2021 ◽  
Author(s):  
Irfete S. Fetahu ◽  
Sabine Taschner-Mandl
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Disease Diagnosis ◽  
Dna Methyltransferases ◽  
Epigenetic Alterations ◽  
Aberrant Expression ◽  
Tet Proteins ◽  
Relative Paucity ◽  
Underlying Causes ◽  
Aberrant Dna Methylation

AbstractNeuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system and one of the most common solid tumors in infancy. Amplification of MYCN, copy number alterations, numerical and segmental chromosomal aberrations, mutations, and rearrangements on a handful of genes, such as ALK, ATRX, TP53, RAS/MAPK pathway genes, and TERT, are attributed as underlying causes that give rise to NB. However, the heterogeneous nature of the disease—along with the relative paucity of recurrent somatic mutations—reinforces the need to understand the interplay of genetic factors and epigenetic alterations in the context of NB. Epigenetic mechanisms tightly control gene expression, embryogenesis, imprinting, chromosomal stability, and tumorigenesis, thereby playing a pivotal role in physio- and pathological settings. The main epigenetic alterations include aberrant DNA methylation, disrupted patterns of posttranslational histone modifications, alterations in chromatin composition and/or architecture, and aberrant expression of non-coding RNAs. DNA methylation and demethylation are mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, respectively, while histone modifications are coordinated by histone acetyltransferases and deacetylases (HATs, HDACs), and histone methyltransferases and demethylases (HMTs, HDMs). This article focuses predominately on the crosstalk between the epigenome and NB, and the implications it has on disease diagnosis and treatment.

scholarly journals Terminal deoxynucleotidyltransferase. Alignment of α- and β-subunits of the core enzyme along the primary translation product

1985 ◽  
Vol 227 (3) ◽  
pp. 1003-1007 ◽  
Author(s):  
C M Beach ◽  
S K Chan ◽  
T C Vanaman ◽  
M S Coleman
Keyword(s):  
Amino Acid ◽  
Nucleotide Sequence ◽  
Amino Acid Sequence ◽  
Beta Subunits ◽  
Isolation And Purification ◽  
C Terminus ◽  
Human Lymphoblast ◽  
Catalytically Active ◽  
Single Polypeptide ◽  
Dna Nucleotide Sequence

Terminal deoxynucleotidyltransferase exists in multiple Mr forms, all apparently generated from a single polypeptide of 62kDa. On isolation and purification, the smallest catalytically active protein of this enzyme consists of two subunits, alpha (12kDa) and beta (30kDa). Recently a complementary-DNA nucleotide sequence has been reported for a portion of the enzyme from human lymphoblast. We have pinpointed the locations of the alpha- and beta-subunits within the elucidated nucleotide sequence. From these data, the portions of the nucleotide sequence coding for the catalytically important area of the transferase can be estimated. Here the amino acid sequence of a number of tryptic peptides from calf alpha- and beta-subunits is presented. Because of the striking homology between the amino acid sequence of the calf enzyme and that predicted for human lymphoblast enzyme, it is possible for us to conclude that the alpha-subunit was generated from the C-terminus of the precursor protein and the beta-subunit was non-overlapping and proximal.

Sign in / Sign up

Export Citation Format

Share Document