Functional and binding studies of HS3.2 of the beta-globin locus control region

Molete, Joseph M.; Petrykowska, Hanna M.; Sigg, Martin; Miller, Webb; Hardison, Ross C.

doi:10.1016/s0378-1119(01)00858-7

Cited by 10 publications

(9 citation statements)

References 33 publications

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“…The beta-globin locus control region (LCR) is a collection of five well-characterized DHSs upstream of the beta-globin genes (Molete et al 2002). The LCR is located near the epsilon-globin gene and has been shown to regulate the other globin genes (HBB/HBD) ;30-50 kb away in erythrocyte but not in brain cell lineages (Tolhuis et al 2002).…”

Section: Beta-globin Locusmentioning

confidence: 99%

“…The LCR is located near the epsilon-globin gene and has been shown to regulate the other globin genes (HBB/HBD) ;30-50 kb away in erythrocyte but not in brain cell lineages (Tolhuis et al 2002). The globin genes are expressed in erythroid cells at different times in development; for example, HBE1 is embryonic, HBG1 and HBG2 are fetal, while HBD and HBB are adult forms (Molete et al 2002). Our study is limited to detecting connections by the cell types we characterized, and the primary cell type driving connections at this locus is K562 (representing undifferentiated erythrocytes), which is known to express the embryonic globin gene HBE1 ( Jackson 2003).…”

Section: Beta-globin Locusmentioning

confidence: 99%

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Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions

et al. 2013

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Regulatory elements recruit transcription factors that modulate gene expression distinctly across cell types, but the relationships among these remains elusive. To address this, we analyzed matched DNase-seq and gene expression data for 112 human samples representing 72 cell types. We first defined more than 1800 clusters of DNase I hypersensitive sites (DHSs) with similar tissue specificity of DNase-seq signal patterns. We then used these to uncover distinct associations between DHSs and promoters, CpG islands, conserved elements, and transcription factor motif enrichment. Motif analysis within clusters identified known and novel motifs in cell-type-specific and ubiquitous regulatory elements and supports a role for AP-1 regulating open chromatin. We developed a classifier that accurately predicts cell-type lineage based on only 43 DHSs and evaluated the tissue of origin for cancer cell types. A similar classifier identified three sex-specific loci on the X chromosome, including the XIST lincRNA locus. By correlating DNase I signal and gene expression, we predicted regulated genes for more than 500K DHSs. Finally, we introduce a web resource to enable researchers to use these results to explore these regulatory patterns and better understand how expression is modulated within and across human cell types.

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Section: Beta-globin Locusmentioning

confidence: 99%

Section: Beta-globin Locusmentioning

confidence: 99%

Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions

et al. 2013

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“…The 15.5-kb sequence and annotations of DHS are from NCBI Reference Sequence: NG_000007.3. HS3.2 was described by Molete et al (53). Repeated elements identified by Repeat Masker are shown in red above the graph and Alu sequences (‘A’) are projected down onto the graph in transparent red.…”

Section: Resultsmentioning

confidence: 99%

Sequence composition similarities with the 7SL RNA are highly predictive of functional genomic features

Paquet¹,

Anderson²

2010

Nucleic Acids Research

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Transposable elements derived from the 7SL RNA gene, such as Alu elements in primates, have had remarkable success in several mammalian lineages. The results presented here show a broad spectrum of functions for genomic segments that display sequence composition similarities with the 7SL RNA gene. Using thoroughly documented loci, we report that DNaseI-hypersensitive sites can be singled out in large genomic sequences by an assessment of sequence composition similarities with the 7SL RNA gene. We apply a root word frequency approach to illustrate a distinctive relationship between the sequence of the 7SL RNA gene and several classes of functional genomic features that are not presumed to be of transposable origin. Transposable elements that show noticeable similarities with the 7SL sequence include Alu sequences, as expected, but also long terminal repeats and the 5′-untranslated regions of long interspersed repetitive elements. In sequences masked for repeated elements, we find, when using the 7SL RNA gene as query sequence, distinctive similarities with promoters, exons and distal gene regulatory regions. The latter being the most notoriously difficult to detect, this approach may be useful for finding genomic segments that have regulatory functions and that may have escaped detection by existing methods.

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“…The system we devised to study position-effect-suppressing elements such as HS6 adds to the somewhat limited array of cell culture approaches that have been utilized to study the activity of LCRs. These include the use of recombination-mediated cassette exchange (51,52), targeted deletion of endogenous sequences in cell lines (53), stable integrated antibiotic resistance markers (54), and cell fusion (55). Continued development of such assays may provide alternatives to time-consuming and expensive transgenic animal models.…”

Section: Discussionmentioning

confidence: 99%

Factors Binding a Non-classical Cis-element Prevent Heterochromatin Effects on Locus Control Region Activity

Harrow

Amuta

Hutchinson

et al. 2004

Journal of Biological Chemistry

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A locus control region (LCR) is a cis-acting gene-regulatory element capable of transferring the expression characteristics of its gene locus of origin to a linked transgene. Furthermore, it can do this independently of the site of integration in the genome of transgenic mice. Although most LCRs contain subelements with classical transcriptional enhancer function, key aspects of LCR activity are supported by cis-acting sequences devoid of the ability to act as direct transcriptional enhancers. Very few of these "non-enhancer" LCR components have been characterized. Consequently, the sequence requirements and molecular bases for their functions, as well as their roles in LCR activity, are poorly understood. We have investigated these questions using the LCR from the mouse T cell receptor (TCR) ␣/Dad1 gene locus. Here we focus on DNase hypersensitive site (HS) 6 of the TCR␣ LCR. HS6 does not support classical enhancer activity, yet has gene regulatory activity in an in vivo chromatin context. We have identified three in vivo occupied factor-binding sites within HS6, two of which interact with Runx1 and Elf-1 factors. Deletion of these sites from the LCR impairs its activity in vivo. This mutation renders the transgene locus abnormally inaccessible in chromatin, preventing the normal function of other LCR subelements and reducing transgene mRNA levels. These data show these factor-binding sites are required for preventing heterochromatin formation and indicate that they function to maintain an active TCR␣ LCR assembly in vivo.

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Functional and binding studies of HS3.2 of the beta-globin locus control region

Cited by 10 publications

References 33 publications

Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions

Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions

Sequence composition similarities with the 7SL RNA are highly predictive of functional genomic features

Factors Binding a Non-classical Cis-element Prevent Heterochromatin Effects on Locus Control Region Activity

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