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In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wrapped into 30-nanometer fibers that form tightly packed chromatin. Histones prevent DNA from becoming tangled and protect it from DNA damage. In addition, histones play important roles in gene regulation and DNA replication. Without histones, unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA if completely stretched out; however, when wound about histones, this length is reduced to about 90 micrometers (0.09 mm) of 30 nm diameter chromatin fibers.
Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the DICER1 gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into short double-stranded RNA fragments called small interfering RNA and microRNA, respectively. These fragments are approximately 20–25 base pairs long with a two-base overhang on the 3′-end. Dicer facilitates the activation of the RNA-induced silencing complex (RISC), which is essential for RNA interference. RISC has a catalytic component Argonaute, which is an endonuclease capable of degrading messenger RNA (mRNA).
The RNA-induced silencing complex, or RISC, is a multiprotein complex, specifically a ribonucleoprotein, which functions in gene silencing via a variety of pathways at the transcriptional and translational levels. Using single-stranded RNA (ssRNA) fragments, such as microRNA (miRNA), or double-stranded small interfering RNA (siRNA), the complex functions as a key tool in gene regulation. The single strand of RNA acts as a template for RISC to recognize complementary messenger RNA (mRNA) transcript. Once found, one of the proteins in RISC, Argonaute, activates and cleaves the mRNA. This process is called RNA interference (RNAi) and it is found in many eukaryotes; it is a key process in defense against viral infections, as it is triggered by the presence of double-stranded RNA (dsRNA).
Charles David Allis was an American molecular biologist, and the Joy and Jack Fishman Professor at the Rockefeller University. He was also the Head of the Laboratory of Chromatin Biology and Epigenetics, and a professor at the Tri-Institutional MD–PhD Program.
RNA-induced transcriptional silencing (RITS) is a form of RNA interference by which short RNA molecules – such as small interfering RNA (siRNA) – trigger the downregulation of transcription of a particular gene or genomic region. This is usually accomplished by posttranslational modification of histone tails which target the genomic region for heterochromatin formation. The protein complex that binds to siRNAs and interacts with the methylated lysine 9 residue of histones H3 (H3K9me2) is the RITS complex.
RNA silencing or RNA interference refers to a family of gene silencing effects by which gene expression is negatively regulated by non-coding RNAs such as microRNAs. RNA silencing may also be defined as sequence-specific regulation of gene expression triggered by double-stranded RNA (dsRNA). RNA silencing mechanisms are conserved among most eukaryotes. The most common and well-studied example is RNA interference (RNAi), in which endogenously expressed microRNA (miRNA) or exogenously derived small interfering RNA (siRNA) induces the degradation of complementary messenger RNA. Other classes of small RNA have been identified, including piwi-interacting RNA (piRNA) and its subspecies repeat associated small interfering RNA (rasiRNA).
The Cancer Genome Atlas (TCGA) is a project to catalogue the genetic mutations responsible for cancer using genome sequencing and bioinformatics. The overarching goal was to apply high-throughput genome analysis techniques to improve the ability to diagnose, treat, and prevent cancer through a better understanding of the genetic basis of the disease.
The history of life on Earth traces the processes by which living and fossil organisms evolved, from the earliest emergence of life to present day. Earth formed about 4.5 billion years ago and evidence suggests that life emerged prior to 3.7 Ga. Although there is some evidence of life as early as 4.1 to 4.28 Ga, it remains controversial due to the possible non-biological formation of the purported fossils.
RNA polymerase IV is an enzyme that synthesizes small interfering RNA (siRNA) in plants, which silence gene expression. RNAP IV belongs to a family of enzymes that catalyze the process of transcription known as RNA Polymerases, which synthesize RNA from DNA templates. Discovered via phylogenetic studies of land plants, genes of RNAP IV are thought to have resulted from multistep evolution processes that occurred in RNA Polymerase II phylogenies. Such an evolutionary pathway is supported by the fact that RNAP IV is composed of 12 protein subunits that are either similar or identical to RNA polymerase II, and is specific to plant genomes. Via its synthesis of siRNA, RNAP IV is involved in regulation of heterochromatin formation in a process known as RNA directed DNA Methylation (RdDM).
The Institute of Molecular Biotechnology (IMBA) is an independent biomedical research organisation founded by the Austrian Academy of Sciences in cooperation with the pharmaceutical company Boehringer Ingelheim. The institute employs around 250 people from over 40 countries, who perform basic research. IMBA is located at the Vienna BioCenter (VBC) and shares facilities and scientific training programs with the Gregor Mendel Institute of Molecular Plant Biology (GMI) of the Austrian Academy of Sciences and the Research Institute of Molecular Pathology (IMP), the basic research center of Boehringer Ingelheim.
RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by other names, including co-suppression, post-transcriptional gene silencing (PTGS), and quelling. The detailed study of each of these seemingly different processes elucidated that the identity of these phenomena were all actually RNAi. Andrew Fire and Craig C. Mello shared the 2006 Nobel Prize in Physiology or Medicine for their work on RNAi in the nematode worm Caenorhabditis elegans, which they published in 1998. Since the discovery of RNAi and its regulatory potentials, it has become evident that RNAi has immense potential in suppression of desired genes. RNAi is now known as precise, efficient, stable and better than antisense therapy for gene suppression. Antisense RNA produced intracellularly by an expression vector may be developed and find utility as novel therapeutic agents.
The microprocessor complex is a protein complex involved in the early stages of processing microRNA (miRNA) and RNA interference (RNAi) in animal cells. The complex is minimally composed of the ribonuclease enzyme Drosha and the dimeric RNA-binding protein DGCR8, and cleaves primary miRNA substrates to pre-miRNA in the cell nucleus. Microprocessor is also the smaller of the two multi-protein complexes that contain human Drosha.
H3K4me3 is an epigenetic modification to the DNA packaging protein Histone H3 that indicates tri-methylation at the 4th lysine residue of the histone H3 protein and is often involved in the regulation of gene expression. The name denotes the addition of three methyl groups (trimethylation) to the lysine 4 on the histone H3 protein.
H3K27me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation of lysine 27 on histone H3 protein.
Bradley E. Bernstein is a biologist and Professor of Cell Biology at Harvard Medical School. He is Chair of the Department of Cancer Biology at the Dana–Farber Cancer Institute and the Director of the Broad Institute's Gene Regulation Observatory. He is known for contributions to the fields of epigenetics and cancer biology.
Neil Alexander Steven Brockdorff is a Wellcome Trust Principal Research Fellow and professor in the department of biochemistry at the University of Oxford. Brockdorff's research investigates gene and genome regulation in mammalian development. His interests are in the molecular basis of X-inactivation, the process that evolved in mammals to equalise X chromosome gene expression levels in XX females relative to XY males.
Gregory James Hannon is a professor of molecular cancer biology and director of the Cancer Research UK Cambridge Institute at the University of Cambridge. He is a Fellow of Trinity College, Cambridge while also serving as a director of cancer genomics at the New York Genome Center and an adjunct professor at Cold Spring Harbor Laboratory.
Manolis Kellis is a professor of Computer Science at the Massachusetts Institute of Technology (MIT) in the area of Computational Biology and a member of the Broad Institute of MIT and Harvard. He is the head of the Computational Biology Group at MIT and is a Principal Investigator in the Computer Science and Artificial Intelligence Lab (CSAIL) at MIT.
H4K91ac is an epigenetic modification to the DNA packaging protein histone H4. It is a mark that indicates the acetylation at the 91st lysine residue of the histone H4 protein. No known diseases are attributed to this mark but it might be implicated in melanoma.
Lydia W. S. Finley is an American scientist and an assistant member at the Cell Biology Program at Memorial Sloan Kettering Cancer Center and an assistant professor at Weill Cornell Medical College. Finley is known for her contributions to understanding the metabolic underpinnings of stem cell fate.
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- ↑ "Investigator | Bernstein Laboratory". Bernstein Laboratory |. 2015-04-16. Retrieved 2022-05-15.
- ↑ "Emily Bernstein | Mount Sinai - New York". Mount Sinai Health System. Retrieved 2022-05-15.
- ↑ Bernstein, Emily; Kim, Sang Yong; Carmell, Michelle A; Murchison, Elizabeth P; Alcorn, Heather; Li, Mamie Z; Mills, Alea A; Elledge, Stephen J; Anderson, Kathryn V; Hannon, Gregory J (2003-11-01). "Dicer is essential for mouse development". Nature Genetics. 35 (3): 215–217. doi:10.1038/ng1253. ISSN 1061-4036. PMID 14528307. S2CID 972721.
- ↑ Bernstein, Emily; Caudy, Amy A.; Hammond, Scott M.; Hannon, Gregory J. (2001). "Role for a bidentate ribonuclease in the initiation step of RNA interference". Nature. 409 (6818): 363–366. doi:10.1038/35053110. ISSN 0028-0836. PMID 11201747. S2CID 4371481.
- ↑ Bernstein, Emily; Allis, C. David (2005-07-15). "RNA meets chromatin". Genes & Development. 19 (14): 1635–1655. doi: 10.1101/gad.1324305 . ISSN 0890-9369. PMID 16024654.
- ↑ Bernstein, Emily; Duncan, Elizabeth M.; Masui, Osamu; Gil, Jesus; Heard, Edith; Allis, C. David (2006). "Mouse Polycomb Proteins Bind Differentially to Methylated Histone H3 and RNA and Are Enriched in Facultative Heterochromatin". Molecular and Cellular Biology. 26 (7): 2560–2569. doi:10.1128/MCB.26.7.2560-2569.2006. ISSN 0270-7306. PMC 1430336 . PMID 16537902.
- ↑ Ooi, Steen K. T.; Qiu, Chen; Bernstein, Emily; Li, Keqin; Jia, Da; Yang, Zhe; Erdjument-Bromage, Hediye; Tempst, Paul; Lin, Shau-Ping; Allis, C. David; Cheng, Xiaodong (2007). "DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA". Nature. 448 (7154): 714–717. Bibcode:2007Natur.448..714O. doi:10.1038/nature05987. ISSN 0028-0836. PMC 2650820 . PMID 17687327.
- ↑ Gaspar-Maia, Alexandre; Qadeer, Zulekha A.; Hasson, Dan; Ratnakumar, Kajan; Adrian Leu, N.; Leroy, Gary; Liu, Shichong; Costanzi, Carl; Valle-Garcia, David; Schaniel, Christoph; Lemischka, Ihor (2013-06-26). "MacroH2A histone variants act as a barrier upon reprogramming towards pluripotency". Nature Communications. 4 (1): 1565. Bibcode:2013NatCo...4.1565G. doi:10.1038/ncomms2582. ISSN 2041-1723. PMC 4055026 . PMID 23463008.
- ↑ Vardabasso, Chiara; Hasson, Dan; Ratnakumar, Kajan; Chung, Chi-Yeh; Duarte, Luis F.; Bernstein, Emily (2014). "Histone variants: emerging players in cancer biology". Cellular and Molecular Life Sciences. 71 (3): 379–404. doi:10.1007/s00018-013-1343-z. ISSN 1420-682X. PMC 4025945 . PMID 23652611.
- ↑ Chicas, Agustin; Kapoor, Avnish; Wang, Xiaowo; Aksoy, Ozlem; Evertts, Adam G.; Zhang, Michael Q.; Garcia, Benjamin A.; Bernstein, Emily; Lowe, Scott W. (2012-06-05). "H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence". Proceedings of the National Academy of Sciences. 109 (23): 8971–8976. Bibcode:2012PNAS..109.8971C. doi: 10.1073/pnas.1119836109 . ISSN 0027-8424. PMC 3384172 . PMID 22615382.
- ↑ Sosa, Maria Soledad; Parikh, Falguni; Maia, Alexandre Gaspar; Estrada, Yeriel; Bosch, Almudena; Bragado, Paloma; Ekpin, Esther; George, Ajish; Zheng, Yang; Lam, Hung-Ming; Morrissey, Colm (2015). "NR2F1 controls tumour cell dormancy via SOX9- and RARβ-driven quiescence programmes". Nature Communications. 6 (1): 6170. Bibcode:2015NatCo...6.6170S. doi:10.1038/ncomms7170. ISSN 2041-1723. PMC 4313575 . PMID 25636082.
- ↑ Strub, Thomas; Ghiraldini, Flavia G.; Carcamo, Saul; Li, Man; Wroblewska, Aleksandra; Singh, Rajendra; Goldberg, Matthew S.; Hasson, Dan; Wang, Zichen; Gallagher, Stuart J.; Hersey, Peter (2018). "SIRT6 haploinsufficiency induces BRAFV600E melanoma cell resistance to MAPK inhibitors via IGF signalling". Nature Communications. 9 (1): 3440. Bibcode:2018NatCo...9.3440S. doi:10.1038/s41467-018-05966-z. ISSN 2041-1723. PMC 6109055 . PMID 30143629.
- ↑ "Scientists discover gene mutation that signals aggressive melanoma". ScienceDaily. April 6, 2022. Retrieved 2022-05-15.
- ↑ Carcamo, Saul; Nguyen, Christie B.; Grossi, Elena; Filipescu, Dan; Alpsoy, Aktan; Dhiman, Alisha; Sun, Dan; Narang, Sonali; Imig, Jochen; Martin, Tiphaine C.; Parsons, Ramon (2022-04-05). "Altered BAF occupancy and transcription factor dynamics in PBAF-deficient melanoma". Cell Reports. 39 (1): 110637. doi:10.1016/j.celrep.2022.110637. ISSN 2211-1247. PMC 9013128 . PMID 35385731.
- ↑ Benson, Barbara (May 5, 2014). "Wall Street funds cancer-research up-and-comers". Crain's New York Business; New York. Vol. 30, no. 18. p. 22 – via ProQuest.