Recruitment of Transcription Complexes to the β-Globin Gene Locus in Vivo and in Vitro

Vieira, Karen; Levings, Padraic P.; Hill, Meredith A.; Crusselle, Valerie J.; Kang, Sung Hae L.; Engel, James Douglas; Bungert, Jörg

doi:10.1074/jbc.m408883200

Cited by 64 publications

(85 citation statements)

References 42 publications

(47 reference statements)

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“…Moreover, Pol II occupancy at the promoter decreased 30-40% in p45/NF-E2-null mice, whereas Pol II occupancy at the LCR remained unchanged (Kooren et al, 2007). Biochemical analysis supports the feasibility of long-range Pol II transfer (Vieira et al, 2004).…”

Section: P45/nf-e2supporting

confidence: 48%

Transcriptional control of erythropoiesis: emerging mechanisms and principles

Kim

2007

Oncogene

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Section: P45/nf-e2supporting

confidence: 48%

Transcriptional control of erythropoiesis: emerging mechanisms and principles

Kim

2007

Oncogene

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“…LCRs may recruit transcription factors and components of the transcription preinitiation complex, including RNA polymerase II, that are subsequently transferred to the promoter region (25,32,47). Our finding that Pol II is bound to HS3 in the 5Ј HS cluster and the promoter region in WT mast cells and BMMC isolated from W sh/sh and BAC200-Kit-GFP transgenic mice, but not in the promoter of the GFP-negative BMMC isolated from W sh/sh , BAC30-Kit-GFP, and BAC200-⌬5ЈHS-Kit-GFP mice, is consistent with such a mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…RNA polymerase II has been reported to associate with distal upstream transcriptional control elements in several model systems (25,42,47). A long-range transfer mechanism in which Pol II is first recruited to the upstream regulatory element and then transferred to the promoter has been proposed.…”

Section: T39 and T71) And Two Lines With Bac200⌬5јhs-kit-gfp (T78 Amentioning

confidence: 99%

A Distant Upstream Locus Control Region Is Critical for Expression of the Kit Receptor Gene in Mast Cells

Berrozpe¹,

Agosti²,

Tucker³

et al. 2006

Molecular and Cellular Biology

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The Kit receptor tyrosine kinase functions in hematopoiesis, melanogenesis, and gametogenesis and in interstitial cells of Cajal. We previously identified two upstream hypersensitive site (HS) clusters in mast cells and melanocytes. Here we investigated the roles of these 5 HS sequences in Kit expression using transgenic mice carrying Kit-GFP reporter constructs. In these mice there is close correspondence between Kit-GFP reporter and endogenous Kit gene expression in most tissues analyzed. Deletion analysis defined the 5 upstream HS cluster region as critical for Kit expression in mast cells. Furthermore, chromatin immunoprecipitation analysis in mast cells showed that H3 and H4 histone hyperacetylation and RNA polymerase II recruitment within the Kit promoter and in the 5 HS region were associated with Kit expression. Therefore, the 5 upstream hypersensitivity sites appear to be critical components of locus control region-mediated Kit gene activation in mast cells.Differential control of gene expression during embryonic development and in the adult organism is mediated by the interaction of the transcription machinery with cis regulatory elements located at the promoter, upstream, or in intronic sequences of a gene. The mechanism by which tissue-specific gene expression is achieved involves the action of transcription factors together with changes in chromatin structure. Chromatin structure is a major determinant of gene expression, and mechanisms of chromatin remodeling are critical components of its regulation. Whereas SWI/SNF-like chromatin-remodeling ATPases disrupt histone-DNA interactions, covalent Nterminal histone modifications, including acetylation, methylation, and phosphorylation, also have important roles in the remodeling of chromatin structure and the regulation of transcription (36). In this way histone modification patterns have been proposed to constitute a histone "code" which specifies downstream functions (45). Hyperacetylation and hypoacetylation of histones H3 and H4 correlate with open/accessible or closed/inaccessible chromatin structures, respectively, and transcriptional activation or repression (22, 31). Thus, the characterization of histone modification patterns has become an important tool in studies of gene expression.The Kit receptor tyrosine kinase (RTK) functions in distinct cell populations during embryonic development and in the postnatal animal (5, 6). During gametogenesis, Kit is expressed in primordial germ cells as they migrate from the allantois to the genital ridge (10, 35). Subsequently, during postnatal gametogenesis, Kit is expressed in spermatogonia and oocytes and in endocrine Leydig and thecal cells (2). In hematopoiesis during embryogenesis and in postnatal animals, Kit is expressed in hematopoietic stem cells and lineage progenitors, as well as in mast cells and eosinophils (5, 18, 48). In melanogenesis, Kit is expressed in migrating melanoblasts during embryonic development, in differentiated melanocytes in hair follicles, and in the gastrointestinal tract in ...

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“…Previous studies have shown that Pol II interacts with LCR HS2 and with the adult β-globin gene promoter and that the binding increases on induction of MEL cell differentiation (26)(27)(28)(29). As shown in Fig.…”

Section: Resultsmentioning

confidence: 89%

Neutralizing the function of a β-globin–associated cis -regulatory DNA element using an artificial zinc finger DNA-binding domain

Barrow

Masannat

Bungert

2012

Proc. Natl. Acad. Sci. U.S.A.

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Gene expression is primarily regulated by cis-regulatory DNA elements and trans-interacting proteins. Transcription factors bind in a DNA sequence-specific manner and recruit activities that modulate the association and activity of transcription complexes at specific genes. Often, transcription factors belong to families of related proteins that interact with similar DNA sequences. Furthermore, genes are regulated by multiple, sometimes redundant, cis-regulatory elements. Thus, the analysis of the role of a specific DNA regulatory sequence and the interacting proteins in the context of intact cells is challenging. In this study, we designed and functionally characterized an artificial DNA-binding domain that neutralizes the function of a cis-regulatory DNA element associated with adult β-globin gene expression. The zinc finger DNA-binding domain (ZF-DBD), comprising six ZFs, interacted specifically with a CACCC site located 90 bp upstream of the transcription start site (-90 β-ZF-DBD), which is normally occupied by KLF1, a major regulator of adult β-globin gene expression. Stable expression of the -90 β-ZF-DBD in mouse erythroleukemia cells reduced the binding of KLF1 with the β-globin gene, but not with locus control region element HS2, and led to reduced transcription. Transient transgenic embryos expressing the -90 β-ZF-DBD developed normally but revealed reduced expression of the adult β-globin gene. These results demonstrate that artificial DNA-binding proteins lacking effector domains are useful tools for studying and modulating the function of cis-regulatory DNA elements.artificial transcription factor | red cell | gene regulation

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Recruitment of Transcription Complexes to the β-Globin Gene Locus in Vivo and in Vitro

Cited by 64 publications

References 42 publications

Transcriptional control of erythropoiesis: emerging mechanisms and principles

Transcriptional control of erythropoiesis: emerging mechanisms and principles

A Distant Upstream Locus Control Region Is Critical for Expression of the Kit Receptor Gene in Mast Cells

Neutralizing the function of a β-globin–associated cis -regulatory DNA element using an artificial zinc finger DNA-binding domain

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