Редактирование: HELLS

Lymphoid-specific helicase (EC 3.6.4.-) (Proliferation-associated SNF2-like protein) (SWI/SNF2-related matrix-associated actin-dependent regulator of chromatin subfamily A member 6) [PASG] [SMARCA6] [Nbla10143]

==Publications==

{{medline-entry
|title=The Ubiquitin-like with PHD and Ring Finger Domains 1 ([[UHRF1]])/DNA Methyltransferase 1 ([[DNMT1]]) Axis Is a Primary Regulator of Cell Senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28100769
|abstract=As senescence develops, cells sequentially acquire diverse senescent phenotypes along with simultaneous multistage gene reprogramming. It remains unclear what acts as the key regulator of the collective changes in gene expression at initiation of senescent reprogramming. Here we analyzed time series gene expression profiles obtained in two different senescence models in human diploid fibroblasts: replicative senescence and H O -induced senescence. Our results demonstrate that suppression of DNA methyltransferase 1 ([[DNMT1]])-mediated DNA methylation activity was an initial event prior to the display of senescent phenotypes. We identified seven [[DNMT1]]-interacting proteins, ubiquitin-like with PHD and ring finger domains 1 ([[UHRF1]]), [[EZH2]], [[CHEK1]], [[SUV39H1]], [[CBX5]], [[PARP1]], and [[HELLS]] (also known as LSH (lymphoid-specific helicase) 1), as being commonly down-regulated at the same time point as [[DNMT1]] in both senescence models. Knockdown experiments revealed that, among the [[DNMT1]]-interacting proteins, only [[UHRF1]] knockdown suppressed [[DNMT1]] transcription. However, [[UHRF1]] overexpression alone did not induce [[DNMT1]] expression, indicating that [[UHRF1]] was essential but not sufficient for [[DNMT1]] transcription. Although [[UHRF1]] knockdown effectively induced senescence, this was significantly attenuated by [[DNMT1]] overexpression, clearly implicating the [[UHRF1]]/[[DNMT1]] axis in senescence. Bioinformatics analysis further identified [[WNT5A]] as a downstream effector of [[UHRF1]]/[[DNMT1]]-mediated senescence. Senescence-associated hypomethylation was found at base pairs -1569 to -1363 from the transcription start site of the [[WNT5A]] gene in senescent human diploid fibroblasts. As expected, [[WNT5A]] overexpression induced senescent phenotypes. Overall, our results indicate that decreased [[UHRF1]] expression is a key initial event in the suppression of [[DNMT1]]-mediated DNA methylation and in the consequent induction of senescence via increasing [[WNT5A]] expression.
|mesh-terms=* CCAAT-Enhancer-Binding Proteins
* Cellular Senescence
* DNA (Cytosine-5-)-Methyltransferase 1
* DNA (Cytosine-5-)-Methyltransferases
* DNA Methylation
* Fibroblasts
* Gene Expression Profiling
* Gene Expression Regulation
* HEK293 Cells
* Histones
* Humans
* Hydrogen Peroxide
* Male
* Oligonucleotide Array Sequence Analysis
* Phenotype
* Promoter Regions, Genetic
* Protein Binding
* Protein Domains
* RNA, Small Interfering
* Ubiquitin-Protein Ligases
* Wnt-5a Protein
* beta-Galactosidase
|keywords=* DNA methylation
* cellular senescence
* gene expression
* gene regulation
* microarray
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339756
}}
{{medline-entry
|title=Age-specific gene expression signatures for breast tumors and cross-species conserved potential cancer progression markers in young women.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23704896
|abstract=Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, [[CCNB2]], [[UBE2C]], [[TOP2A]], [[CEP55]], [[TPX2]], [[BIRC5]], KIAA0101, [[SHCBP1]], [[UBE2T]], [[PTTG1]], [[NUSAP1]], [[DEPDC1]], [[HELLS]], [[CCNB1]], [[KIF4A]], and [[RRM2]], that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies.
|mesh-terms=* Adult
* Aging
* Animals
* Biomarkers, Tumor
* Breast Neoplasms
* Carcinogenesis
* Carcinoma, Ductal, Breast
* Carcinoma, Intraductal, Noninfiltrating
* Cohort Studies
* Computational Biology
* Disease Progression
* Female
* Gene Expression Regulation, Neoplastic
* Gene Regulatory Networks
* Genes, Neoplasm
* Genome, Human
* Humans
* Immunohistochemistry
* Mice
* Middle Aged
* Oligonucleotide Array Sequence Analysis
* Reproducibility of Results
* Species Specificity
* Transcriptome
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660335
}}