Lysine demethylases KDM6A and UTY: The X and Y of histone demethylation

Publication date: Available online 6 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Iveta Gažová, Andreas Lengeling, Kim M. SummersAbstractHistone demethylases remove transcriptional repressive marks from histones in the nucleus. KDM6A (also known as UTX) is a lysine demethylase which acts on the trimethylated lysine at position 27 in histone 3. The KDM6A gene is located on the X chromosome but escapes X inactivation even though it is not located in the pseudoautosomal region. There is a homologue of KDM6A on the Y chromosome, known as UTY. UTY was thought to have lost its demethylase activity and to represent a non-functional remnant of the ancestral KDM6A gene. However, results with knockout mice suggest that the gene is expressed and the protein performs some function within the cell. Female mice with homozygous deletion of Kdm6a do not survive, but hemizygous males are viable, attributed to the presence of the Uty gene. KDM6A is mutated in the human condition Kabuki syndrome type 2 (OMIM 300867) and in many cases of cancer. The amino acid sequence of KDM6A has been conserved across animal phyla, although it is only found on the X chromosome in eutherian mammals. In this review, we reanalyse existing data from various sources (protein sequence comparison, evolutionary genetics, transcription factor binding and gene expression analysis) to determine the function, expression and evolution of KDM6A and UTY and show that UTY has a functional role similar t...
Source: Molecular Genetics and Metabolism - Category: Genetics & Stem Cells Source Type: research

Related Links:

According to the American Cancer Society, cancer screening increases the chance of detecting certain cancers early, when they might be easier to treat. More good news from the National Cancer Institute shows that cancer survival rates are at an all-time high and cancer-related deaths are declining. Experts are attributing the improved outcomes to treatment advances, prevention awareness efforts — and screenings. Fortunately, today’s imagi ng technology provides an important tool in the fight…
Source: Health Care:Pharmaceuticals headlines - Category: Pharmaceuticals Authors: Source Type: news
When should immunotherapy be considered in patients with NSCLC and actionable driver mutations?Annals of Oncology
Source: Medscape Today Headlines - Category: Consumer Health News Tags: Hematology-Oncology Journal Article Source Type: news
Roche today announced that results from a number of studies across its comprehensive oncology portfolio, covering a broad range of cancers including bladder, lung and breast will be presented at the European Society for Medical Oncology (ESMO) 2019 Congress, taking place from 27 September - 1 October in Barcelona, Spain.
Source: Roche Media News - Category: Pharmaceuticals Source Type: news
Source: Cancer Management and Research - Category: Cancer & Oncology Tags: Cancer Management and Research Source Type: research
This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed.
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
1. The breast is the most heavily guarded and protected part of a woman ’s body. This means there is good reason to worry less. Did you know that a mammogram is one of only two imaging tests (the other being a low-dose lung cancer screening for former or current heavy smokers) paid for by insurance companies in the U.S. for asymptomatic patients without any risk facto rs? It is the only part of a woman’s body which gets scrutinized every year. Finding breast cancer early (stage 1: less than…
Source: Health Care:Pharmaceuticals headlines - Category: Pharmaceuticals Authors: Source Type: news
Source: OncoTargets and Therapy - Category: Cancer & Oncology Tags: OncoTargets and Therapy Source Type: research
A 3-year-old Japanese girl treated for hypoplastic left heart syndrome and Dandy-Walker syndrome was diagnosed with Kabuki syndrome (KS) with a mutation of KMT2D; c.13285C>T:p.Q4429*. Concurrently, macrohematuria portended the diagnosis of Wilms tumor. Postoperative chemotherapy has achieved complete remission despite a prolonged and reduced regimen due to liver dysfunction and convulsions. Cancer predisposition has been suggested for KS due to oncogenic mutations in KMT2D or KDM6A. The first case of nephroblastoma exemplified the treatability of malignancies in KS patients, as shown in the 9 cases reviewed. Active scre...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Original Articles Source Type: research
Abstract Histone-lysine N-methyltransferase 2D (KMT2D), also known as MLL4 and MLL2 in humans and Mll4 in mice, belongs to a family of mammalian histone H3 lysine 4 (H3K4) methyltransferases. It is a large protein over 5500 amino acids in size and is partially functionally redundant with KMT2C. KMT2D is widely expressed in adult tissues and is essential for early embryonic development. The C-terminal SET domain is responsible for its H3K4 methyltransferase activity and is necessary for maintaining KMT2D protein stability in cells. KMT2D associates with WRAD (WDR5, RbBP5, ASH2L, and DPY30), NCOA6, PTIP, PA1, and H3...
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research
Conclusion: Kabuki syndrome is not considered a cancer predisposition syndrome. Nonetheless, a number of tumors have been reported in patients with Kabuki syndrome. Spinal ependymoma is a rare disease in the pediatric and young adult population. Whereas NF2 mutations are frequently associated to ependymoma such an association has never been described in Kabuki syndrome. To our knowledge this is the first case of ependymoma in a KMT2D mutated Kabuki syndrome patient. Despite KMT2D role in cancer has previously been described, no genetic data are available for previously reported Kabuki syndrome patients with tumors. Nonethe...
Source: BMC Medical Genetics - Category: Genetics & Stem Cells Authors: Source Type: research
More News: Cancer | Cancer & Oncology | Genetics | Kabuki Syndrome