Neil Brockdorff | |
---|---|
Born | Neil Alexander Steven Brockdorff 1958 (age 64–65) [1] |
Education | Hampstead School [1] |
Alma mater | University of Sussex (BSc) University of Glasgow (PhD) [2] |
Awards | EMBO Member (1999) [3] |
Scientific career | |
Fields | Developmental epigenetics X inactivation [4] |
Institutions | University of Oxford |
Thesis | The effect of oestradiol-17β on the ribonucleases and ribonuclease inhibitor of immature rat uterus (1985) |
Website | www |
Neil Alexander Steven Brockdorff FRS FMedSci FRSB [5] (born 1958) is a Wellcome Trust Principal Research Fellow and professor in the department of biochemistry at the University of Oxford. [6] [7] Brockdorff's research investigates gene and genome regulation in mammalian development. [8] 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. [8]
Brockdorff was educated at Hampstead School, the University of Sussex (BSc) [1] and the University of Glasgow (PhD). [2]
X inactivation is an important model for understanding how epigenetic mechanisms, for example modification of DNA and histone proteins around which DNA is packaged, contribute to gene regulation in developmental biology. [8] [9] In earlier work Brockdorff demonstrated that an unusual functional RNA molecule, XIST, controls the X inactivation process. [10] [11] Building on this finding he has elucidated key steps in XIST gene regulation during early development, and has defined major pathways through which XIST RNA induces chromosome wide gene silencing. [8] [12] [13] [14]
Brockdorff is a member of the European Molecular Biology Organization (EMBO), a Fellow of the Royal Society (FRS), a Fellow of the Academy of Medical Sciences (FMedSci) and a Fellow of the Royal Society of Biology (FRSB).
A Barr body or X-chromatin is an inactive X chromosome. In species with XY sex-determination, females typically have two X chromosomes, and one is rendered inactive in a process called lyonization. Errors in chromosome separation can also result in male and female individuals with extra X chromosomes. The Lyon hypothesis states that in cells with multiple X chromosomes, all but one are inactivated early in embryonic development in mammals. The X chromosomes that become inactivated are chosen randomly, except in marsupials and in some extra-embryonic tissues of some placental mammals, in which the X chromosome from the sperm is always deactivated.
Heterochromatin is a tightly packed form of DNA or condensed DNA, which comes in multiple varieties. These varieties lie on a continuum between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a role in the expression of genes. Because it is tightly packed, it was thought to be inaccessible to polymerases and therefore not transcribed; however, according to Volpe et al. (2002), and many other papers since, much of this DNA is in fact transcribed, but it is continuously turned over via RNA-induced transcriptional silencing (RITS). Recent studies with electron microscopy and OsO4 staining reveal that the dense packing is not due to the chromatin.
Dosage compensation is the process by which organisms equalize the expression of genes between members of different biological sexes. Across species, different sexes are often characterized by different types and numbers of sex chromosomes. In order to neutralize the large difference in gene dosage produced by differing numbers of sex chromosomes among the sexes, various evolutionary branches have acquired various methods to equalize gene expression among the sexes. Because sex chromosomes contain different numbers of genes, different species of organisms have developed different mechanisms to cope with this inequality. Replicating the actual gene is impossible; thus organisms instead equalize the expression from each gene. For example, in humans, female (XX) cells randomly silence the transcription of one X chromosome, and transcribe all information from the other, expressed X chromosome. Thus, human females have the same number of expressed X-linked genes per cell as do human males (XY), both sexes having essentially one X chromosome per cell, from which to transcribe and express genes.
X-inactivation is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into a transcriptionally inactive structure called heterochromatin. As nearly all female mammals have two X chromosomes, X-inactivation prevents them from having twice as many X chromosome gene products as males, who only possess a single copy of the X chromosome.
Mary Frances Lyon was an English geneticist best known for her discovery of X-chromosome inactivation, an important biological phenomenon.
Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells.
Polycomb-group proteins are a family of protein complexes first discovered in fruit flies that can remodel chromatin such that epigenetic silencing of genes takes place. Polycomb-group proteins are well known for silencing Hox genes through modulation of chromatin structure during embryonic development in fruit flies. They derive their name from the fact that the first sign of a decrease in PcG function is often a homeotic transformation of posterior legs towards anterior legs, which have a characteristic comb-like set of bristles.
Core histone macro-H2A.1 is a protein that in humans is encoded by the H2AFY gene.
Xist is a non-coding RNA on the X chromosome of the placental mammals that acts as a major effector of the X-inactivation process. It is a component of the Xic – X-chromosome inactivation centre – along with two other RNA genes and two protein genes.
Long non-coding RNAs are a type of RNA, generally defined as transcripts more than 200 nucleotides that are not translated into protein. This arbitrary limit distinguishes long ncRNAs from small non-coding RNAs, such as microRNAs (miRNAs), small interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and other short RNAs. Given that some lncRNAs have been reported to have the potential to encode small proteins or micro-peptides, the latest definition of lncRNA is a class of RNA molecules of over 200 nucleotides that have no or limited coding capacity. Long intervening/intergenic noncoding RNAs (lincRNAs) are sequences of lncRNA which do not overlap protein-coding genes.
RoX RNA is a non-coding RNA (ncRNA) present in the male-specific lethal (MSL) complex and is required for sex dosage compensation in Drosophila. As males only contain one X chromosome, male flies dosage compensate for the X chromosome by hyper-transcribing the X chromosome. This is achieved by the MSL complex binding to the X chromosome and inducing histone H4 lysine 16 acetylation and allows for the formation of euchromatin. These ncRNAs were first discovered in RNA extracted from neuronal cells.
Tsix is a non-coding RNA gene that is antisense to the Xist RNA. Tsix binds Xist during X chromosome inactivation. The name Tsix comes from the reverse of Xist, which stands for X-inactive specific transcript.
Edith Heard is a British-French researcher in epigenetics and since January 2019 has been the Director General of the European Molecular Biology Laboratory (EMBL). She is also Professor at the Collège de France, holding the Chair of Epigenetics and Cellular Memory. From 2010 to 2018, Heard was the Director of the Genetics and Developmental Biology department at the Curie Institute (Paris), France. Heard is noted for her studies of X-chromosome-inactivation.
Epigenetics of human development is the study of how epigenetics effects human development.
Wendy Anne Bickmore is a British genome biologist known for her research on the organisation of genomic material in cells.
X chromosome inactivation (XCI) is the phenomenon that has been selected during the evolution to balance X-linked gene dosage between XX females and XY males.
Jeannie T. Lee is a Professor of Genetics at Harvard Medical School and the Massachusetts General Hospital, and a Howard Hughes Medical Institute Investigator. She is known for her work on X-chromosome inactivation and for discovering the functions of a new class of epigenetic regulators known as long noncoding RNAs (lncRNAs), including Xist and Tsix.
Anne Jacqueline Ridley is professor of Cell Biology and Head of School for Cellular and Molecular Medicine at the University of Bristol. She was previously a professor at King's College London.
X chromosome reactivation (XCR) is the process by which the inactive X chromosome (the Xi) is re-activated in the cells of eutherian female mammals. Therian female mammalian cells have two X chromosomes, while males have only one, requiring X-chromosome inactivation (XCI) for sex-chromosome dosage compensation. In eutherians, XCI is the random inactivation of one of the X chromosomes, silencing its expression. Much of the scientific knowledge currently known about XCR comes from research limited to mouse models or stem cells.
Bruce Macintosh Cattanach FRS was a British mouse geneticist, known for his pioneering work in the fields of autosomal imprinting and X chromosome inactivation.
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