Developmental control via GATA factor interplay at chromatin domains

Bresnick, Emery H.; Martowicz, Melissa L.; Pal, Shantanu; Johnson, Kirby D.

doi:10.1002/jcp.20393

Cited by 93 publications

(75 citation statements)

References 129 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…GATA factors have unique and overlapping functions (54)(55)(56) and can elicit opposite transcriptional responses through common chromatin sites (56). GATA-3, STAT6, and BRG1 occupy the repressed T H 2 locus, in which an LCR associates with the promoters in a ''poised'' configuration (53).…”

Section: Discussionmentioning

confidence: 99%

BRG1 requirement for long-range interaction of a locus control region with a downstream promoter

Kim

Bultman

Kiefer

et al. 2009

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

Self Cite

115

109

View full text Add to dashboard Cite

The dynamic packaging of DNA into chromatin is a fundamental step in the control of diverse nuclear processes. Whereas certain transcription factors and chromosomal components promote the formation of higher-order chromatin loops, the co-regulator machinery mediating loop assembly and disassembly is unknown. Using mice bearing a hypomorphic allele of the BRG1 chromatin remodeler, we demonstrate that the Brg1 mutation abrogated a cell type-specific loop between the ␤-globin locus control region and the downstream ␤major promoter, despite trans-acting factor occupancy at both sites. By contrast, distinct loops were insensitive to the Brg1 mutation. Molecular analysis with a conditional allele of GATA-1, a key regulator of hematopoiesis, in a novel cell-based system provided additional evidence that BRG1 functions early in chromatin domain activation to mediate looping. Although the paradigm in which chromatin remodelers induce nucleosome structural transitions is well established, our results demonstrating an essential role of BRG1 in the genesis of specific chromatin loops expands the repertoire of their functions.chromatin ͉ erythroid ͉ GATA-1 ͉ globin ͉ transcription I ntegral to the developmental emergence of specialized cell types is the establishment of cell type-specific chromatin structures. Early studies developed important concepts regarding the impact of nucleosome positioning on protein-chromatin interactions (1), and more recently, ChIP technology (2) ushered in an explosive increase in information on the distribution of histone modifications and nucleosomes genome-wide (3). However, many questions remain unanswered regarding how higher-order chromatin structures are established and regulated.Nucleosomal filaments assemble into 30-nm fibers, which fold into higher-order loops (4). Chromosome conformation capture (3C) (5) studies have provided evidence for looping in response to trans-acting factor binding to chromatin (6-10). Key regulators of erythropoiesis-GATA-1 (11, 12), erythroid Krüppel-like factor (EKLF) (13), and the GATA-1-coregulator friend of GATA-1 (FOG-1) (14)-induce looping at the ␤-globin locus, in which the proximity of the locus control region (LCR) relative to a distant promoter increases (15, 16). The E-protein-interacting factor NL1/ Ldb1 also occupies the LCR and promotes looping (17). However, the role of chromatin modifying and remodeling co-regulators in looping is largely unexplored.Histone acetylation counteracts higher-order folding of chromatin templates in vitro (18), and broad acetylation characterizes active chromatin domains (19,20). Thus, it seems likely that histone acetylases and deacetylases are components of the looping machinery. As methylation of histone H3 at lysine 9 serves as a ligand that mediates heterochromatin protein 1 binding during heterochromatin assembly (21-23), the relevant methyltransferases might control looping. Although chromatin remodeling complexes, such as switch/sucrose nonfermentable (SWI/SNF), induce nucleosome structural transitions and a...

show abstract

Section: Discussionmentioning

confidence: 99%

BRG1 requirement for long-range interaction of a locus control region with a downstream promoter

Kim

Bultman

Kiefer

et al. 2009

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

Self Cite

115

109

View full text Add to dashboard Cite

show abstract

“…GATA factor chromatin occupancy is likely to be regulated by GATA motif features, chromatin, neighboring cis elements, and GATA factor concentration (23,24). GATA-1 DNA binding activity is 10-fold greater in primitive vs. definitive chicken erythroid cells (25), although the consequence of this difference vis-à-vis chromatin occupancy is unknown.…”

mentioning

confidence: 99%

Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles

Johnson

Kim

Boyer

et al. 2007

Blood Cells, Molecules, and Diseases

Self Cite

View full text Add to dashboard Cite

“…In a number of these cases, the transcriptional onset and decline of a series of closely related genes are tightly and sequentially controlled, a process that is critical for attaining the correct genotypic readout and proper phenotypic effect (2)(3)(4). A particularly wellstudied example of this process is the developmental control of the hemoglobin proteins, particularly those encoded by the genes within the ß-like globin locus (5,6).…”

mentioning

confidence: 99%

Design of embedded chimeric peptide nucleic acids that efficiently enter and accurately reactivate gene expression in vivo

Chen

Peterson²,

Iancu‐Rubin³

et al. 2010

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

View full text Add to dashboard Cite

Pharmacological treatments designed to reactivate fetal γ-globin can lead to an effective and successful clinical outcome in patients with hemoglobinopathies. However, new approaches remain highly desired because such treatments are not equally effective for all patients, and toxicity issues remain. We have taken a systematic approach to develop an embedded chimeric peptide nucleic acid (PNA) that effectively enters the cell and the nucleus, binds to its target site at the human fetal γ-globin promoter, and reactivates this transcript in adult transgenic mouse bone marrow and human primary peripheral blood cells. In vitro and in vivo DNAbinding assays in conjunction with live-cell imaging have been used to establish and optimize chimeric PNA design parameters that lead to successful gene activation. Our final molecule contains a specific γ-promoter-binding PNA sequence embedded within two amino acid motifs: one leads to efficient cell/nuclear entry, and the other generates transcriptional reactivation of the target. These embedded PNAs overcome previous limitations and are generally applicable to the design of in vivo transcriptional activation reagents that can be directed to any promoter region of interest and are of direct relevance to clinical applications that would benefit from such a need.γ-globin gene reactivation | primary human CD34+ cells

show abstract

Developmental control via GATA factor interplay at chromatin domains

Cited by 93 publications

References 129 publications

BRG1 requirement for long-range interaction of a locus control region with a downstream promoter

BRG1 requirement for long-range interaction of a locus control region with a downstream promoter

Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles

Design of embedded chimeric peptide nucleic acids that efficiently enter and accurately reactivate gene expression in vivo

Contact Info

Product

Resources

About