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Oliver Rando

Genomic approaches to chromatin structure and function, and to epigenetic inheritance.

Public data sets:
http://users.umassmed.edu/Oliver.Rando/

Organisms sharing identical genomes may nonetheless exhibit heritable variation in traits that are now called “epigenetic” traits. Information carriers for epigenetic traits include prion conformation and cytosine methylation, and it is widely believed that the packaging of eukaryotic genomes into chromatin provides another carrier of epigenetic information. Epigenetics is of great interest for researchers interested in fields ranging from systems biology to evolution to human disease.

Our lab is broadly interested in epigenetic inheritance, but most of our research focuses on one putative carrier of epigenetic information – the nucleoprotein complex known as chromatin. We utilize “genomics” tools such as DNA microarrays and high-throughput sequencing to measure chromatin structure over entire genomes at single-nucleosome resolution, with the eventual goal of determining how chromatin states are established and maintained.

We consider the primary sequence of chromatin to consist of three major features – the positioning of nucleosomes relative to underlying genomic sequence, the covalent modification pattern of each nucleosome, and the histone variants comprising each histone octamer. To date, we have measured these three features in actively growing yeast cultures, and have also measured the exchange rates of histone H3 in G1-arrested yeast. A number of interesting features emerge from these studies:

Most interesting, we have identified what may be considered “motifs” in chromatin structure in yeast. For example, yeast promoters are characterized by a nucleosome-free region (NFR) of about 140 bp flanked by two well-positioned nucleosomes that lack a number of modifications such as H4K16ac, and that are rapidly replaced throughout the cell cycle. The +1 nucleosome also tends to carry Htz1 in place of H2A, while the -1 nucleosome carries Htz1 at a subset of promoters.

Another interesting feature of yeast chromatin is that covalent modifications tend to occur in a small number of highly-correlated groups, suggesting that histone modification patterns do not encode complex “messages.” Nonetheless, the abundance of covalent modifications (over 100 have been described!!!) raises the question of why so many exist.

By measuring histone replacement dynamics, we have found that coding regions are surprisingly “cold”, meaning the passage of RNA polymerase does not result in nucleosome replacement except at extremely high transcription rates. Heterochromatin is also cold, while promoter and tRNA genes are associated with hot nucleosomes. Chromatin boundaries – sequences whose presence prevents the lateral spread of silencing complexes from a nucleating element – are also associated with rapidly-exchanged nucleosomes, suggesting that “scrubbing” or chromatin by rapid replacement serves as the mechanism to limit this lateral spreading.

Our lab is interested in the following questions:

1) What are the rules by which chromatin motifs are generated? How do genomic sequences, and factors such as RNA polymerase passage, result in the common chromatin patterns seen at so many genes?

2) What are the mechanisms resulting in replication-independent histone replacement?

3) What are there so many histone modifications? What are the “systems” features that result from histone modification crosstalk?

4) More generally, how does chromatin act as a signal filter in cells, given its location between upstream signaling pathways and downstream transcriptional outcomes?

5) What happens to nucleosomes during genomic replication, and how do old nucleosomes influence the states of newly-incorporated nucleosomes? What is the machinery required to maintain a chromatin state?

6) How does chromatin structure change over evolution, and how do chromatin regulators contribute to phenotypic divergence in closely-related species?

7) What phenotypes are epigenetically heritable, and under what conditions is a selective advantage conferred by stochastic switching as opposed to plastic responsiveness to the environment?

8) How is the genome packaged in sperm and embryonic stem cells, and how do histone dynamics change during differentiation?

Rotation Projects

Rotation projects are available to study chromatin structure and function.

Project 1. Measure histone dynamics in yeast.

Histone dynamics play major roles in chromatin metabolism and in the inheritance of chromatin states. To measure histone replacement rates in yeast, we have created yeast strains carrying inducible epitope-tagged histones H3 and H2A. Using microarrays, we will measure histone replacement rates in a variety of mutant yeast to ascertain the role of various chromatin remodeling factors in histone exchange reactions.

Project 2. Characterize mechanisms for epigenetic inheritance in yeast.

We have identified a variety of genes whose expression state in yeast is epigenetically heritable. We will screen the yeast genome for genes that affect the inheritance of these expression patterns.

Project 3. Measure histone dynamics in embryonic stem cells.

Embryonic stem cells are pluripotent cells that can give rise to every type of cell in the adult animal. The role of chromatin structure in maintaining this pluripotent state is poorly understood, but it appears that stem cell chromatin is exceptionally labile relative to that in differentiated cells. We will create stem cell lines with inducible tagged histones to measure histone replacement rates across the mouse genome.


One or more keywords matched the following items that are connected to Rando, Oliver

Item TypeName
Academic Article Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation.
Academic Article Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling.
Academic Article Second messenger control of chromatin remodeling.
Academic Article The yeast Rat1 exonuclease promotes transcription termination by RNA polymerase II.
Academic Article Genomic characterization reveals a simple histone H4 acetylation code.
Academic Article Developmentally induced changes in transcriptional program alter spatial organization across chromosomes.
Academic Article Single-nucleosome mapping of histone modifications in S. cerevisiae.
Academic Article Searching for a function for nuclear actin.
Academic Article Noisy silencing of chromatin.
Academic Article Global patterns of histone modifications.
Academic Article Dynamics of replication-independent histone turnover in budding yeast.
Academic Article Rules and regulation in the primary structure of chromatin.
Academic Article Chromatin remodelling at promoters suppresses antisense transcription.
Academic Article A biologist despairs over the difficulty of demonstrating heritability of chromatin states.
Academic Article Cell cycle- and chaperone-mediated regulation of H3K56ac incorporation in yeast.
Academic Article Genome-wide views of chromatin structure.
Academic Article Nucleosome positioning: how is it established, and why does it matter?
Academic Article Chromatin 'programming' by sequence--is there more to the nucleosome code than %GC?
Academic Article Phosphatidylinositol-dependent actin filament binding by the SWI/SNF-like BAF chromatin remodeling complex.
Academic Article Recent evidence for pervasive adaptation targeting gene expression attributable to population size change.
Academic Article The role of nucleosome positioning in the evolution of gene regulation.
Academic Article Control of chromatin structure by spt6: different consequences in coding and regulatory regions.
Academic Article Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals.
Academic Article Evolutionary divergence of intrinsic and trans-regulated nucleosome positioning sequences reveals plastic rules for chromatin organization.
Academic Article Sub1 and RPA associate with RNA polymerase II at different stages of transcription.
Academic Article A key role for Chd1 in histone H3 dynamics at the 3' ends of long genes in yeast.
Academic Article A functional evolutionary approach to identify determinants of nucleosome positioning: a unifying model for establishing the genome-wide pattern.
Academic Article Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors.
Academic Article Daddy issues: paternal effects on phenotype.
Academic Article Painting by numbers: increasing the parts list for chromatin domains.
Academic Article Toward a unified physical model of nucleosome patterns flanking transcription start sites.
Academic Article A histone acetylation switch regulates H2A.Z deposition by the SWR-C remodeling enzyme.
Academic Article Histone variant H2A.Z marks the 5' ends of both active and inactive genes in euchromatin.
Academic Article Distinct pathways for snoRNA and mRNA termination.
Academic Article Chromatin structure in the genomics era.
Academic Article Timescales of genetic and epigenetic inheritance.
Academic Article Independent and complementary methods for large-scale structural analysis of mammalian chromatin.
Academic Article Oliver Rando: taking chromatin analysis to the genomic scale. Interview by Ruth Williams.
Academic Article Activity motifs reveal principles of timing in transcriptional control of the yeast metabolic network.
Academic Article High-resolution nucleosome mapping reveals transcription-dependent promoter packaging.
Academic Article Chromatin as a potential carrier of heritable information.
Academic Article RNA polymerase mapping during stress responses reveals widespread nonproductive transcription in yeast.
Academic Article Overlapping regulation of CenH3 localization and histone H3 turnover by CAF-1 and HIR proteins in Saccharomyces cerevisiae.
Academic Article Global regulation of H2A.Z localization by the INO80 chromatin-remodeling enzyme is essential for genome integrity.
Academic Article Genome-wide measurement of histone H3 replacement dynamics in yeast.
Academic Article Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells.
Academic Article Chromatin and transcription in yeast.
Academic Article Combinatorial complexity in chromatin structure and function: revisiting the histone code.
Academic Article NURDs are required for diversity.
Academic Article Systematic dissection of roles for chromatin regulators in a yeast stress response.
Concept Gene Expression Regulation, Fungal
Concept Chromatin Immunoprecipitation
Concept Chromatin
Concept Gene Expression Regulation, Developmental
Concept Gene Expression Regulation
Concept Chromatin Assembly and Disassembly
Academic Article Mechanisms underlying nucleosome positioning in vivo.
Academic Article High-resolution mapping of chromatin packaging in mouse embryonic stem cells and sperm.
Academic Article A system for genome-wide histone variant dynamics in ES cells reveals dynamic MacroH2A2 replacement at promoters.
Academic Article Suppression of pervasive noncoding transcription in embryonic stem cells by esBAF.
Academic Article High-resolution chromatin dynamics during a yeast stress response.
Academic Article Epigenomics and the structure of the living genome.
Academic Article Chromatin Dynamics and the RNA Exosome Function in Concert to Regulate Transcriptional Homeostasis.
Academic Article R loops regulate promoter-proximal chromatin architecture and cellular differentiation.
Academic Article Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.
Academic Article Regulation of X-linked gene expression during early mouse development by Rlim.
Academic Article Small RNAs Gained during Epididymal Transit of Sperm Are Essential for Embryonic Development in Mice.
Academic Article Effects of Larval Density on Gene Regulation in Caenorhabditis elegans During Routine L1 Synchronization.
Academic Article Transcriptome-wide Analysis of Roles for tRNA Modifications in Translational Regulation.
Academic Article LINE-1 activation after fertilization regulates global chromatin accessibility in the early mouse embryo.
Academic Article Condensin-Dependent Chromatin Compaction Represses Transcription Globally during Quiescence.
Academic Article Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding.
Academic Article Mesoscale organization of the chromatin fiber.

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  • Regulation