Heterochromatin dysregulation in human diseases

Hahn, Matthias; Dambacher, Silvia; Schotta, Gunnar

doi:10.1152/japplphysiol.00053.2010

Cited by 36 publications

(30 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FRG1 is a gene that has been proven to be associated with the disease of facioscapulohumeral muscular dystrophy (FSHD) . FRG1 is located in the region close to a large array of repetitive sequences (D4Z4), which possess characteristics of CpG islands .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of age‐related somatic mutation profiles in Chinese young lung adenocarcinoma patients

Yang

et al. 2019

Cancer Medicine

View full text Add to dashboard Cite

Background Lung adenocarcinoma in young adults is a rare entity with the oncogenic genetic alterations associated being poorly understood. In the present study, the effect of genetic alterations in lung adenocarcinoma patients diagnosed in young patients is reported. Methods Twenty young lung adenocarcinoma patients (age years: median: 33.5, range: 24‐36) were enrolled in the current study and 24 patients who were at common age of the disease onset (age years: median: 61.5, range: 52‐79) were selected for comparison. Paraffin sections of lung adenocarcinoma were analyzed using the whole‐exome sequencing platform. Results Similar number of somatic mutations per tumor were found in the young patients and their older counterparts. Although no age‐related differences were detected in the numbers of lung adenocarcinoma patients harboring well‐known gene variants, mutations in FRG1 and KMT2C were associated with a younger age especially after correcting for tobacco smoking and sex (FRG1: P = 0.027, KMT2C: P = 0.046). Five genetic variants showed higher alteration frequencies in young patients compared to the unclassified East Asian population, suggesting these mutations as disease‐related hereditary germline variants. Conclusions These results suggest different characteristics of lung adenocarcinoma between the young and the patients at common age of onset. Young patients with lung adenocarcinoma have a distinctly unique prevalence of oncogenic genetic alterations.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of age‐related somatic mutation profiles in Chinese young lung adenocarcinoma patients

Yang

et al. 2019

Cancer Medicine

View full text Add to dashboard Cite

show abstract

“…Dysregulation of pericentric heterochromatin has been suggested to play important roles in cancer development and progression (Hahn et al 2010;Zhu et al 2011). Cancer cells are frequently characterized by genomic instability and cohesion defects (Thompson et al 2010), but the mechanisms are still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Pericentric heterochromatin is largely transcriptionally inert but serves important functions in ensuring genomic stability and accurate chromosome segregation Ting et al 2011;Zhu et al 2011). Thus, dysregulation of heterochromatin organization leads to severe diseases and developmental defects (Hahn et al 2010).…”

mentioning

confidence: 99%

Suv4-20h2 mediates chromatin compaction and is important for cohesin recruitment to heterochromatin

et al. 2013

Self Cite

View full text Add to dashboard Cite

Cohesin plays an important role in chromatid cohesion and has additional functions in higher-order chromatin organization and in transcriptional regulation. The binding of cohesin to euchromatic regions is largely mediated by CTCF or the mediator complex. However, it is currently unknown how cohesin is recruited to pericentric heterochromatin in mammalian cells. Here we define the histone methyltransferase Suv4-20h2 as a major structural constituent of heterochromatin that mediates chromatin compaction and cohesin recruitment. Suv4-20h2 stably associates with pericentric heterochromatin through synergistic interactions with multiple heterochromatin protein 1 (HP1) molecules, resulting in compaction of heterochromatic regions. Suv4-20h mutant cells display an overall reduced chromatin compaction and an altered chromocenter organization in interphase referred to as ''chromocenter scattering.'' We found that Suv4-20h-deficient cells display chromosome segregation defects during mitosis that coincide with reduced sister chromatid cohesion. Notably, cohesin subunits interact with Suv4-20h2 both in vitro and in vivo. This interaction is necessary for cohesin binding to heterochromatin, as Suv4-20h mutant cells display substantially reduced cohesin levels at pericentric heterochromatin. This defect is most prominent in G0-phase cells, where cohesin is virtually lost from heterochromatin, suggesting that Suv4-20h2 is involved in the initial loading or maintenance of cohesion subunits. In summary, our data provide the first compelling evidence that Suv4-20h2 plays essential roles in regulating nuclear architecture and ensuring proper chromosome segregation.

show abstract

“…Recently, an increasing number of studies have reported that chromatin accessibility is associated with diseases such as Huntington's disease [31], muscular dystrophy [32], breast cancer [33] and pancreatic cancer [34], reflecting its importance in biology. Our method is the first one to use a diploid genome and FAIRE-seq to discover motifs associated with chromatin accessibility, which leads to the first chromatin motif database (CMD).…”

Section: Discussionmentioning

confidence: 99%

Discovering chromatin motifs using FAIRE sequencing and the human diploid genome

et al. 2013

View full text Add to dashboard Cite

BackgroundSpecific chromatin structures are associated with active or inactive gene transcription. The gene regulatory elements are intrinsically dynamic and alternate between inactive and active states through the recruitment of DNA binding proteins, such as chromatin-remodeling proteins.ResultsWe developed a unique genome-wide method to discover DNA motifs associated with chromatin accessibility using formaldehyde-assisted isolation of regulatory elements with high-throughput sequencing (FAIRE-seq). We aligned the FAIRE-seq reads to the GM12878 diploid genome and subsequently identified differential chromatin-state regions (DCSRs) using heterozygous SNPs. The DCSR pairs represent the locations of imbalances of chromatin accessibility between alleles and are ideal to reveal chromatin motifs that may directly modulate chromatin accessibility. In this study, we used DNA 6-10mer sequences to interrogate all DCSRs, and subsequently discovered conserved chromatin motifs with significant changes in the occurrence frequency. To investigate their likely roles in biology, we studied the annotated protein associated with each of the top ten chromatin motifs genome-wide, in the intergenic regions and in genes, respectively. As a result, we found that most of these annotated motifs are associated with chromatin remodeling, reflecting their significance in biology.ConclusionsOur method is the first one using fully phased diploid genome and FAIRE-seq to discover motifs associated with chromatin accessibility. Our results were collected to construct the first chromatin motif database (CMD), providing the potential DNA motifs recognized by chromatin-remodeling proteins and is freely available at http://syslab.nchu.edu.tw/chromatin.

show abstract

Heterochromatin dysregulation in human diseases

Cited by 36 publications

References 101 publications

Comprehensive analysis of age‐related somatic mutation profiles in Chinese young lung adenocarcinoma patients

Comprehensive analysis of age‐related somatic mutation profiles in Chinese young lung adenocarcinoma patients

Suv4-20h2 mediates chromatin compaction and is important for cohesin recruitment to heterochromatin

Discovering chromatin motifs using FAIRE sequencing and the human diploid genome

Contact Info

Product

Resources

About