Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II

Zhang, He; Niu, Beibei; Hu, Ji-Fan; Ge, Shengfang; Wang, Haibo; Li, Tao; Ling, Jianqun; Steelman, Brandon N.; Qian, Guofeng; Hoffman, Andrew R.

doi:10.1083/jcb.201101021

Cited by 64 publications

(79 citation statements)

References 47 publications

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“…Total protein extracts of cultured cells in each group were prepared using nuclear and cytoplasmic extraction reagents (Pierce, Rockford, Ill., USA) as previously described [Zhang et al, 2011]. The protein concentration was measured using BCA Protein Assay Reagent (Pierce).…”

Section: Western Blot Analysismentioning

confidence: 99%

Conditioned Medium from Bone Marrow Mesenchymal Stem Cells Transiently Retards Osteoblast Differentiation by Downregulating Runx2

Sun

Zhou

Deng

et al. 2012

Cells Tissues Organs

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Mesenchymal stem cells (MSCs) are attractive candidates for cell therapy and regenerative medicine because of their potential for proliferation and multilineage differentiation. MSCs secrete various cytokines, acting as trophic mediators to regulate neighboring cells. Osteoblasts are the cells directly responsible for forming new bone, and they are the final target of many osteogenic regulators. However, the induction effect of MSCs on osteoblasts is still unknown. In this study, we isolated osteoblasts from rat calvariae and investigated their proliferation and differentiation under induction of varied concentrations of MSC-conditioned medium (MSC-CM). Cells in the MSC-CM groups showed a reduction in cell proliferation at 3–6 days, and a decrease in the expression of osteocalcin and osteopontin at 3 days, with low levels of alkaline phosphatase activity. The expression of osteogenic markers went back to normal at 7 days. In order to evaluate the molecular mechanisms underlying this suppression, levels of two osteoblastic transcription factors, runt-related transcription factor 2 (Runx2) and osterix (Osx), were detected at both mRNA and protein levels. The results indicated that MSC-CM significantly inhibited Runx2 expression in a concentration-dependent manner. However, the effect was not due to the inhibition of Osx, for Osx was not significantly altered. This work demonstrates that MSCs may suppress osteoblast proliferation and transiently retard osteoblast differentiation by downregulating Runx2. These results highlight the need to take into account the paracrine effect of MSCs when using them in regenerative medicine for the repair of bone defects.

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Section: Western Blot Analysismentioning

confidence: 99%

Conditioned Medium from Bone Marrow Mesenchymal Stem Cells Transiently Retards Osteoblast Differentiation by Downregulating Runx2

Sun

Zhou

Deng

et al. 2012

Cells Tissues Organs

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“…This activity is attributable to the presence of binding sites within the DMD for the vertebrate insulator protein, CTCF. As inferred by chromatin conformation capture assays, the CTCF-bound maternal DMD causes the locus to adopt a three-dimensional conformation, which occludes the activation of Igf2 by the enhancers, leading to the activation of H19 expression (Engel et al 2006;Kurukuti et al 2006;Zhang et al 2011). Importantly, association of CTCF with its binding sites is inhibited by the presence of DNA methylation.…”

Section: X-chromosome Inactivation: a Model For The Establishment Of mentioning

confidence: 99%

Genomic Imprinting and Epigenetic Control of Development

Fedoriw

Mugford²,

Magnuson

2012

Cold Spring Harbor Perspectives in Biology

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SUMMARYEpigenetic mechanisms are extensively utilized during mammalian development. Specific patterns of gene expression are established during cell fate decisions, maintained as differentiation progresses, and often augmented as more specialized cell types are required. Much of what is known about these mechanisms comes from the study of two distinct epigenetic phenomena: genomic imprinting and X-chromosome inactivation. In the case of genomic imprinting, alleles are expressed in a parent-of-origin-dependent manner, whereas X-chromosome inactivation in females requires that only one X chromosome is active in each somatic nucleus. As model systems for epigenetic regulation, genomic imprinting and X-chromosome inactivation have identified and elucidated the numerous regulatory mechanisms that function throughout the genome during development.

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“…57 Abolishing this ability of CTCF decreased H3K27 methylation, compromised DNA loop formation and reactivated the normally suppressed maternal IGF2 allele. 56 Whether direct interactions between cohesin and PRC2 exist to regulate loop formation and histone methylation remains unclear. Future studies should clarify relationships between cohesin, CTCF, lncRNA, PRC2 and other factors as well as identify the relative contribution of all of these molecules to chromatin looping and histone post-translational modifications across the genome.…”

confidence: 99%

“…In addition, a recent study demonstrated the involvement of the polycomb repressive complex-2 (PRC2) in loop formation at IGF2-H19. 56 Once recruited to IGF2-H19 in a CTCF-dependent fashion, PRC2 methylates histone H3 lysine 27 (H3K27) within the promoter region of the maternal IGF2 allele to ensure its efficient silencing. 57 Abolishing this ability of CTCF decreased H3K27 methylation, compromised DNA loop formation and reactivated the normally suppressed maternal IGF2 allele.…”

confidence: 99%

Cohesin and related coiled-coil domain-containing complexes physically and functionally connect the dots across the genome

Poon

Mekhail

2011

Cell Cycle

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Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II

Abstract: CCCTC binding factor (CTCF) mutants that cannot bind components of the polycomb repressive complex-2 (PRC2) do not form the chromatin loops that regulate monoallelic gene expression.

Cited by 64 publications

References 47 publications

Conditioned Medium from Bone Marrow Mesenchymal Stem Cells Transiently Retards Osteoblast Differentiation by Downregulating Runx2

Conditioned Medium from Bone Marrow Mesenchymal Stem Cells Transiently Retards Osteoblast Differentiation by Downregulating Runx2

Genomic Imprinting and Epigenetic Control of Development

Cohesin and related coiled-coil domain-containing complexes physically and functionally connect the dots across the genome

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