Distinct HP1 and Su(var)3-9 complexes bind to sets of developmentally coexpressed genes depending on chromosomal location

Greil, Frauke; Kraan, Ineke van der; Delrow, Jeffrey J.; Smothers, James; Wit, Elzo de; Bussemaker, Harmen J.; Driel, Roel van; Henikoff, Steven; Steensel, Bas van

doi:10.1101/gad.281503

Cited by 157 publications

(211 citation statements)

References 49 publications

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“…In fact, the Drosophila data suggests the formation of a static domain, perhaps through the use of insulators, that delimits the local effect on expression. A recent genomic analysis of HP1 and Su(var)3-9 binding supports a domain architecture of gene expression, as developmentally regulated genes display uniform patterns of association with one or both of the proteins (Greil et al 2003). Either by a spreading of modifications or the establishment of a domain, it is interesting that looping from CTs (as described above) appears to correlate with the range of effect seen at the genomic level (Ragoczy et al 2003).…”

Section: Genomic Organization Of Cellular Differentiation Genes and Devmentioning

confidence: 94%

Form follows function: the genomic organization of cellular differentiation

Kosak¹,

Groudine²

2004

Genes Dev.

218

179

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The extent to which the nucleus is functionally organized has broad biological implications. Evidence supports the idea that basic nuclear functions, such as transcription, are structurally integrated within the nucleus. Moreover, recent studies indicate that the linear arrangement of genes within eukaryotic genomes is nonrandom. We suggest that determining the relationship between nuclear organization and the linear arrangement of genes will lead to a greater understanding of how transcriptomes, dedicated to a particular cellular function or fate, are coordinately regulated. Current network theories may provide a useful framework for modeling the inherent complexity the functional organization of the nucleus.Louis Sullivan, whose early efforts helped pioneer the development of the skyscraper, is considered one of the most important architects of the last century. However, it is his dictum-"form ever follows function"-for which he is perhaps best known. Just as this imperative has influenced generations of architects, the idea that structure reflects function provides a useful perspective for a biologist's view of the cell. In many ways, the structure and function of cellular and subcellular organelles are inseparable; that is, disruptions in organelle function can lead to perturbations in its structure. Upon inhibition of rRNA transcription, for example, the nucleolus becomes disordered and ultimately disappears (Leung and Lamond 2003). This integration of structure and cellular function allows for conservation of resources and facilitates regulation at multiple levels.Although a completely sequenced genome may represent a genetic blueprint, molecular biologists currently lack a key with which to fully grasp how this sequence is related to the development and subsequent maintenance of a given organism. Following Sullivan's example, a comprehensive understanding of genomic sequence may require considering its arrangement in the nucleus; the form DNA takes in the nucleus reveals not only its higher-order structure, but it may impart information regarding its function. The current paradigm of gene regulation includes the binding of site-specific transcription factors, the recruitment of cofactors and general transcription factors, and the incorporation of multiple modifications to both the DNA and the histones that organize it (Felsenfeld and Groudine 2003). This description of transcription belies its enormous complexity, fueled by an ever-increasing catalog of proteins dedicated in one way or another to its regulation. Additionally, evidence supporting the role of nuclear localization in transcriptional regulation indicates that it is insufficient to know the components of transcription . Rather, a thorough understanding of the process requires knowing its functional organization within the nucleus. In this sense, transcription should not be viewed simply as a process that turns on a specific gene, but as a process that governs within the genome an entire network of genes (a transcriptome) that gives rise to a p...

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Section: Genomic Organization Of Cellular Differentiation Genes and Devmentioning

confidence: 94%

Form follows function: the genomic organization of cellular differentiation

Kosak¹,

Groudine²

2004

Genes Dev.

218

179

View full text Add to dashboard Cite

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“…But many fruit fly genes have been found to inhabit pericentric heterochromatin at low density 40 , where they are expressed despite association with heterochromatin proteins 41 . The same appears to be true for Arabidopsis, in which one study mapped genes to a transposon-rich region thought at the time to be within centromeric DNA 20 .…”

Section: Discussionmentioning

confidence: 99%

Sequencing of a rice centromere uncovers active genes

Nagaki

Cheng

Ouyang³

et al. 2004

Nat Genet

Self Cite

487

525

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Centromeres are the last frontiers of complex eukaryotic genomes, consisting of highly repetitive sequences that resist mapping, cloning and sequencing. The centromere of rice Chromosome 8 (Cen8) has an unusually low abundance of highly repetitive satellite DNA, which allowed us to determine its sequence. A region of ∼750 kb in Cen8 binds rice CENH3, the centromere-specific H3 histone. CENH3 binding is contained within a larger region that has abundant dimethylation of histone H3 at Lys9 (H3-Lys9), consistent with Cen8 being embedded in heterochromatin. Fourteen predicted and at least four active genes are interspersed in Cen8, along with CENH3 binding sites. The retrotransposons located in and outside of the CENH3 binding domain have similar ages and structural dynamics. These results suggest that Cen8 may represent an intermediate stage in the evolution of centromeres from genic regions, as in human neocentromeres, to fully mature centromeres that accumulate megabases of homogeneous satellite arrays.

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“…This view has recently been challenged on several fronts with evidence of highly dynamic regulation and lively complex reassembly. For instance, recent data suggest important functions outside heterochromatin and point to Suv39-independent functions of HP1 members and vice versa (Greil et al 2003). Further more, photobleaching experiments using fluorochrome-tagged HP1 demonstrated that the majority of the HP1 proteins are highly mobile with rapid movements in and out of heterochromatin domains (Festenstein et al 2003;Schmiedeberg et al 2004).…”

Section: Stability and Dynamics Of Epigenetic Gene Regulationmentioning

confidence: 99%

Epigenetics and cancer

Lund¹,

Lohuizen²

2004

Genes Dev.

442

318

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Epigenetic mechanisms act to change the accessibility of chromatin to transcriptional regulation locally and globally via modifications of the DNA and by modification or rearrangement of nucleosomes. Epigenetic gene regulation collaborates with genetic alterations in cancer development. This is evident from every aspect of tumor biology including cell growth and differentiation, cell cycle control, DNA repair, angiogenesis, migration, and evasion of host immunosurveillance. In contrast to genetic cancer causes, the possibility of reversing epigenetic codes may provide new targets for therapeutic intervention.Epigenetic programming is crucial in mammalian development, and stable inheritance of epigenetic settings is essential for the maintenance of tissue-and cell-typespecific functions (Li 2002). With the exception of controlled genomic rearrangements, such as those of the immunoglobulin and T-cell receptor genes in B and T cells, all other differentiation processes are initiated or maintained through epigenetic processes. Not surprisingly therefore, epigenetic gene regulation is characterized overall by a high degree of integrity and stability. Evidence is accumulating that suggests that the intrinsic stability is caused by multiple interlocking feedback mechanisms between functionally unrelated epigenetic layers, such as DNA methyltransferases (DNMTs) and histone modifying enzymes, resulting in the stable commitment of a locus to a particular activity state. In somatic cells, the transcriptional status of most genes is epigenetically fixed. However, other genes, such as cell cycle checkpoint genes and genes directly affected by exogenous stimuli such as growth factors or cell-cell contact, likely reside in a balanced state sensitive to dynamic adjustments in histone modifications, thereby allowing for rapid responses to specific stimuli. Perturbation of epigenetic balances may lead to alterations in gene expression, ultimately resulting in cellular transformation and malignant outgrowth; the involvement of deregulated epigenetic mechanisms in cancer development has received increased attention in recent years.Per definition, epigenetic regulators alter the activities and abilities of a cell without directly affecting and mutating the sequence of the DNA. In this review, we deal with epigenetic gene regulation as imposed by DNA methylation, covalent modifications of the canonical core histones, deposition of variant histone proteins, local nucleosome remodeling, and long-range epigenetic regulators. Understanding the molecular details behind "epigenetic cancer diseases" holds potentially important prospects for medical treatment, as it allows for novel strategies for drug development. A number of recent reviews have provided details on epigenetic mechanisms and their involvement in cancer, and we refer to these for more in-depth information on individual epigenetic mechanisms

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Distinct HP1 and Su(var)3-9 complexes bind to sets of developmentally coexpressed genes depending on chromosomal location

Cited by 157 publications

References 49 publications

Form follows function: the genomic organization of cellular differentiation

Form follows function: the genomic organization of cellular differentiation

Sequencing of a rice centromere uncovers active genes

Epigenetics and cancer

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