Proximity among Distant Regulatory Elements at the β-Globin Locus Requires GATA-1 and FOG-1

Vakoc, Christopher R.; Letting, Danielle L.; Gheldof, Nele; Sawado, Tomoyuki; Bender, Michael A.; Groudine, Mark; Weiss, Mitchell J.; Dekker, Job; Blobel, Gerd A.

doi:10.1016/j.molcel.2004.12.028

Cited by 468 publications

(461 citation statements)

References 47 publications

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“…This largescale chromatin change represses the expression of many developmental genes (Isono et al, 2005;Boyer et al, 2006;Lee et al, 2006;Lanzuolo et al, 2007;Sing et al, 2009). Another group of proteins, the GATA factors, regulate the conformation of chromatin, influencing gene expression (Vakoc et al, 2005). For example, at the Kit locus, the exchange of GATA proteins causes the formation of different chromatin loops that affect transcriptional activity (Jing et al, 2008).…”

Section: The Unknown Spatial Distribution Of Cis-regulatory Informationmentioning

confidence: 99%

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Frankel

2012

Developmental Dynamics

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Genomes contain the necessary information to ensure that genes are expressed in the right place, at the right time, and with the proper rate. Metazoan developmental genes often possess long stretches of DNA flanking their coding sequences and/or large introns which contain elements that influence gene expression. Most of these regulatory elements are relatively small and can be studied in isolation. For example, transcriptional enhancers, the elements that generate the expression pattern of a gene, have been traditionally studied with reporter constructs in transgenic animals. These studies have provided and will provide invaluable insights into enhancer evolution and function. However, this experimental approach has its limits; often, enhancer elements do not faithfully recapitulate native expression patterns. This fact suggests that additional information in cis-regulatory regions modulates the activity of enhancers and other regulatory elements. Indeed, recent studies have revealed novel functional aspects at the level of whole cis-regulatory regions. First, the discovery of ''shadow enhancers.'' Second, the ubiquitous interactions between cis-regulatory elements. Third, the notion that some cis-regulatory regions may not function in a modular manner. Last, the effect of chromatin conformation on cis-regulatory activity. In this article, I describe these recent findings and discuss open questions in the field.

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Section: The Unknown Spatial Distribution Of Cis-regulatory Informationmentioning

confidence: 99%

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Frankel

2012

Developmental Dynamics

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“…3C technology was applied to a cell line containing a GATA-1-fusion protein that is localized in the cytoplasm, but upon stimulation is rapidly recruited to the nucleus (27). When GATA-1 is located in the cytoplasm, looping between the promoter of b maj and HS2 and HS3 is nearly absent.…”

Section: Gata-1 and Fog-1mentioning

confidence: 99%

Joining the loops: β‐Globin gene regulation

Noordermeer

Laat

2008

IUBMB Life

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SummaryThe mammalian b-globin locus is a multigene locus containing several globin genes and a number of regulatory elements. During development, the expression of the genes changes in a process called ''switching.'' The most important regulatory element in the locus is the locus control region (LCR) upstream of the globin genes that is essential for high-level expression of these genes. The discovery of the LCR initially raised the question how this element could exert its effect on the downstream globin genes. The question was solved by the finding that the LCR and activate globin genes are in physical contact, forming a chromatin structure named the active chromatin hub (ACH). Here we discuss the significance of ACH formation, provide an overview of the proteins implicated in chromatin looping at the b-globin locus, and evaluate the relationship between nuclear organization and b-globin gene expression. IUBMBIUBMB Life, 60(12): 824-833, 2008

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“…Enhancers and locus control regions (LCRs) are long-range regulatory elements that activate promoters in a distance-and orientation-independent manner, and recent studies indicate that enhancers and LCRs often cluster together in three-dimensional space to form an "active chromatin hub" (23,49,58,59).…”

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Long-Range Communication between the Silencers of HMR

Valenzuela

Dhillon

Dubey

et al. 2008

Molecular and Cellular Biology

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Gene regulation involves long-range communication between silencers, enhancers, and promoters. In Saccharomyces cerevisiae, silencers flank transcriptionally repressed genes to mediate regional silencing. Silencers recruit the Sir proteins, which then spread along chromatin to encompass the entire silenced domain. In this report we have employed a boundary trap assay, an enhancer activity assay, chromatin immunoprecipitations, and chromosome conformation capture analyses to demonstrate that the two HMR silencer elements are in close proximity and functionally communicate with one another in vivo. We further show that silencing is necessary for these long-range interactions, and we present models for Sir-mediated silencing based upon these results.Gene activation and gene repression are central to the proper development and differentiation of organisms. DNA elements such as promoters, enhancers, and silencers play a central role in eukaryotic gene regulation. These elements are separated from each other by several kilobase pairs of DNA but are able to communicate with one another to regulate the activation or repression of genes. The exact mechanism by which distally located elements communicate with one another is not clear and is one of the key questions in gene regulation. Long-range communication between distantly located elements in chromosomes is thought to occur by one of two principal mechanisms (8). One class of models postulate that a signal emanating from a distal regulatory element spreads along the DNA fiber until it encounters a proximal regulatory element. A second class of models postulate that distal and proximal regulatory elements interact with one another directly, with the intervening DNA forming a loop. Both mechanisms must function within the context of the global chromosome structure, which appears to be composed of large chromosome loops that attach to a proteinaceous superstructure (11). The nucleus appears to be divided further into distinct chromatin compartments, with heterochromatic domains being present in regions near the nuclear periphery while euchromatic domains are found mainly in the interior of the nucleus, although a significant portion of euchromatin is located near nuclear pores.It has been suggested that the functionally and structurally defined chromatin domains may be coincident (36). Enhancers and locus control regions (LCRs) are long-range regulatory elements that activate promoters in a distance-and orientation-independent manner, and recent studies indicate that enhancers and LCRs often cluster together in three-dimensional space to form an "active chromatin hub" (23,49,58,59).Similarly, in yeast the promoters and terminators of genes are in close proximity to one another (3, 48) and tethered to the nuclear pore (10, 52). The consequence of this spatial organization is that the DNA between these regulatory elements is looped out. It is thought that the formation of these nuclear substructures aids in transcription activation.Silencers are negative regulatory element...

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Proximity among Distant Regulatory Elements at the β-Globin Locus Requires GATA-1 and FOG-1

Cited by 468 publications

References 47 publications

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Multiple layers of complexity in cis‐regulatory regions of developmental genes

Joining the loops: β‐Globin gene regulation

Long-Range Communication between the Silencers of HMR

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