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Cited by 53Genomics and Chromatin DynamicsHemoglobinopathies and Related DisordersNuclear Structure and Function

The hypersensitive sites of the murine β-globin locus control region act independently to affect nuclear localization and transcriptional elongation

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Bender, M. A., Ragoczy, Tobias, Lee, Jongjoo, Byron, Rachel, Telling, Agnes, Dean, Ann, Groudine, Mark·2012·Blood
DOI 10.1182/blood-2011-09-380485PMC PMC3335386
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Abstract

The β-globin locus control region (LCR) is necessary for high-level β-globin gene transcription and differentiation-dependent relocation of the β-globin locus from the nuclear periphery to the central nucleoplasm and to foci of hyperphosphorylated Pol II “transcription factories” (TFys). To determine the contribution of individual LCR DNaseI hypersensitive sites (HSs) to transcription and nuclear location, in the present study, we compared β-globin gene activity and location in erythroid cells derived from mice with deletions of individual HSs, deletions of 2 HSs, and deletion of the whole LCR and found all of the HSs had a similar spectrum of activities, albeit to different degrees. Each HS acts as an independent module to activate expression in an additive manner, and this is correlated with relocation away from the nuclear periphery. In contrast, HSs have redundant activities with respect to association with TFys and the probability that an allele is actively transcribed, as measured by primary RNA transcript FISH. The limiting effect on RNA levels occurs after β-globin genes associate with TFys, at which time HSs contribute to the amount of RNA arising from each burst of transcription by stimulating transcriptional elongation.

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  • Facilitators, as described here, may be relatively common elements in multipartite enhancers.

    “Review of diverse, albeit incomplete, previous analyses of SEs16,17,19,20,22 suggest that facilitators, as described here, may be relatively common elements in multipartite enhancers.”

    From Super-enhancers include classical enhancers and facilitators to fully activate gene expression (2023) · cites this paper as [16]

    The Results and Discussion describe the β-globin locus control region as an array of hypersensitive-site modules with distinct effects on localization and transcription. That provides an example of functional components in a multipartite enhancer, but the paper does not establish that facilitators as defined by the citing authors are relatively common across such enhancers. The relevant passages have no page number in our copy. (LLM, conf=0.76)

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  • A number of groups have dissected super-enhancers, yielding various conclusions, from additive to super-additive, redundant, synergistic, and hierarchical cooperation.

    “A number of groups have dissected SEs, yielding various conclusions, from additive16 to super-additive,22 redundant,19 synergistic,21 and hierarchical20 cooperation.”

    From Super-enhancers include classical enhancers and facilitators to fully activate gene expression (2023) · cites this paper as [16]

  • Previous less extensive studies have shown that the individual regulatory elements of the β-globin LCR behave in a similar independent and additive manner.

    “Previous less extensive studies have also shown that the individual regulatory elements of the β-globin LCR, which we show here also corresponds to an erythroid super-enhancer, behave in a similar independent and additive manner28.”

    From Genetic dissection of the α-globin super-enhancer in vivo (2016) · cites this paper as [28]

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Cites

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Cited by

Sorted by citations

Authors
Bender, M. A., Ragoczy, T., Lee, J., Byron, R., Telling, A., Dean, A., & Groudine, M.
Affiliations
  • University of Washington (US)
  • Fred Hutch Cancer Center (US)
  • National Institutes of Health (US)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2012-04-19
Volume
119
Issue
16
Pages
3820-3827
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2011-09-380485
PMC
PMC3335386
OpenAlex
W2022465811
Cited by
53
References
8
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 14 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 3 · 2013: 4 · 2012: 1
FWCI
1.80
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Cooley's Anemia Foundation
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL065440, HL065440)
  • National Cancer Institute (P30CA015704)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R37DK044746, DK 44746)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
beta-globin locus control region, DNase I hypersensitive sites, transcription elongation, transcription factories, nuclear localization, erythroid cells, beta-globin gene expression, allele-specific transcription, transcriptional activation
MeSH terms
Animals, Cell Nucleus, Mice, Transgenic, RNA, Messenger, Transcription, Genetic, Gene Deletion, Gene Expression Regulation, Developmental, Locus Control Region, Erythroid Cells, Mice, beta-Globins, Nucleoplasmins

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