Reprogramming Factor Expression Initiates Widespread Targeted Chromatin Remodeling

Koche, Richard P.; Smith, Zachary D.; Adli, Mazhar; Gu, Hongcang; Ku, Manching; Gnirke, Andreas; Bernstein, B; Meissner, Alexander

doi:10.1016/j.stem.2010.12.001

Cited by 335 publications

(369 citation statements)

References 23 publications

(35 reference statements)

Supporting

Mentioning

341

Contrasting

Unclassified

Order By: Relevance

“…In addition, PARP1 occupies gene loci such as Nanog and Esrrb to enrich activation‐associated marker histone H3 lysine 4 dimethylation (H3K4me2) in early‐stage reprogramming 11, 30. In addition to our observation that PARP1 interacts with CHD1L, it is plausible that CHD1L may also coregulate the chromatin status of stemness genes, such as Pou5f1, Nanog , and Esrrb , through an interaction with PARP1.…”

Section: Resultsmentioning

confidence: 72%

See 1 more Smart Citation

CHD1L Regulated PARP1-Driven Pluripotency and Chromatin Remodeling During the Early-Stage Cell Reprogramming

Jiang¹,

Chen

et al. 2015

Stem Cells

View full text Add to dashboard Cite

PARP1 and poly(ADP‐ribosyl)ation (PARylation) have been shown to be essential for the initial steps of cellular reprogramming. However, the mechanism underlying PARP1/PARylation‐regulated activation of pluripotency loci remains undetermined. Here, we demonstrate that CHD1L, a DNA helicase, possesses chromatin remodeling activity and interacts with PARP1/PARylation in regulating pluripotency during reprogramming. We found that this interaction is mediated through the interplay of the CHD1L macro‐domain and the PAR moiety of PARylated‐PARP1. Chromatin immunoprecipitation assays demonstrated the co‐occupancy of CHD1L and PARP1 at Pou5f1, Nanog, and Esrrb pluripotency loci. Knockdown of CHD1L significantly blocked the binding activity of PARP1 at pluripotency loci and inhibited the efficiency of PARP1‐driven reprogramming. Notably, we found that CHD1L‐promoted reprogramming requires both a PARP1‐interacting domain and DNA helicase activity, partly contributing to the chromatin‐remodeling states of pluripotency loci. Taken together, these results identify CHD1L as a key chromatin remodeler involved in PARP1/PARylation‐regulated early‐stage reprogramming and pluripotency in stem cells. Stem Cells 2015;33:2961–2972

show abstract

Section: Resultsmentioning

confidence: 72%

“…Pluripotent stemness factors are able to epigenetically reopen the stemness‐related chromatin, leading to efficient nuclear reprogramming 30. Doege et al demonstrated a PARP1‐driven induction of endogenous pluripotency in early reprogramming stages by epigenetically promoting accessibility to OCT4.…”

Section: Introductionmentioning

confidence: 99%

CHD1L Regulated PARP1-Driven Pluripotency and Chromatin Remodeling During the Early-Stage Cell Reprogramming

Jiang¹,

Chen

et al. 2015

Stem Cells

View full text Add to dashboard Cite

show abstract

“…For example, efficient downregulation of somatic gene expression was observed, as was widespread posttranslational modification of histones on the regulatory regions of many of the target genes of Yamanaka factors [59][60][61] .…”

Section: Deterministic or Stochastic?mentioning

confidence: 99%

Mechanisms of nuclear reprogramming by eggs and oocytes: a deterministic process?

Jullien

Pasque²,

Halley-Stott³

et al. 2011

Nat Rev Mol Cell Biol

103

View full text Add to dashboard Cite

Differentiated cells can be experimentally reprogrammed back to pluripotency by nuclear transfer, cell fusion or induced pluripotent stem cell technology. Nuclear transfer and cell fusion can lead to efficient reprogramming of gene expression. The egg and oocyte reprogramming process includes the exchange of somatic proteins for oocyte proteins, the post-translational modification of histones and the demethylation of DNA. These events occur in an ordered manner and on a defined timescale, indicating that reprogramming by nuclear transfer and by cell fusion rely on deterministic processes.The remarkable stability of cell differentiation under normal conditions can be reversed experimentally by nuclear transfer, cell fusion and induced pluripotent stem (iPS) cell technology [1][2][3][4][5] . This provides an opportunity to generate pluripotent embryonic cells from adult cells of the same individual and hence opens the possibilit y of cell replacement without the need for immunosuppression.iPS cell technology makes use of the overexpression of transcription factors (FIG. 1a) and has been extensively reviewed, so it is not discussed in detail [6][7][8][9] . To generate entirely unrelated cell types by iPS cell technology, treated cells must be grown for multiple cell divisions over a long period of time (up to 3 weeks). By contrast, nuclear transfer and cell fusion do not involve the overexpression of new genes, and instead make use of natura components present in eggs and some early embryos to initiate new transcription.There are two kinds of nuclear transfer experiments: egg-NT involves the transfer of a single somatic nucleus to an unfertilize d enucleated egg (in both mammals and amphibians) 1 (FIG. 1b); and ooc-NT involves the transplantation of multiple somatic cell nuclei into the germinal vesicle (the nucleus) of a growing meiotic prophase amphibian oocyte (an immature egg) 10 (FIG. 1c). Note that the terms egg and oocyte refer to different developmental stages in amphibians and mammals: amphibian eggs are in metaphase II of meiosis, which is equivalent to mouse metaphase II stage oocytes, whereas their immediate precursors, oocytes, are blocked in meiotic prophase I, which is equivalent to mouse germinal vesicle stage oocytes.© 2011 Macmillan Publishers Limited. All rights reserved Correspondence to J.B.G.j.gurdon@gurdon.cam.ac.uk. Competing interests statementThe authors declare no competing financial interests. There are important differences between the two types of nuclear transfer experimen t. Extensive cell division takes place in egg-NT experiments, and functional new cell types appear as the nuclear transplant embryo develops. By contrast, in ooc-NT experiments, no new cell types are formed, and neither the oocyte nor the introduced nuclei divide, but there is a direct transition from nuclei of differentiated cells to reprogrammed nuclei that transcribe pluripotency genes. Analysis of the mechanism of reprogramming (which involves transcription of pluripotency and other genes) in egg-NT expe...

show abstract

“…The epigenetic processes preventing gene reactivation are described in more and more details. These includes the methylation of DNA, the incorporation of histone variants as well as the post-translational modifications of histone tails, on the regulatory regions of repressed genes (Koche et al, 2011;Pasque et al, 2011). Nuclear transfer and induced pluripotency both show that some epigenetic marks on chromatin are efficiently modified during reprogramming (Koche et al, 2011;Murata et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Reprogramming of gene expression following nuclear transfer to theXenopusoocyte

Jullien

Gurdon

2011

Biologie Aujourd'hui

View full text Add to dashboard Cite

-Transplantation of Xenopus laevis cell nucleus to enucleated Xenopus egg leads to the generation of cloned animal. This exemplifies the process of nuclear reprogramming by which the nucleus of a specialized cell is reset to an embryonic state from which it can generate all the cells of an organism. Using the precursor of the egg, the oocyte, it is also possible to reprogram somatic cell. The advantage of this approach is the direct reprogramming of gene expression in the absence of cell division. Using this strategy it is possible to investigate the mechanism leading to transcriptional reprogramming of somatic nuclei. By combining real time monitoring of chromatin protein exchange and gene expression analysis, we have observed that a simultaneous loss of somatic H1 linker histone and incorporation of the oocyte-specific linker histone B4 precede transcriptional reprogramming. The loss of H1 is not required for gene reprogramming. We have demonstrated both by antibody injection experiments and by dominant negative interference that the incorporation of B4 linker histone is required for pluripotency gene reactivation during nuclear reprogramming. We suggest that the binding of oocyte specific B4 linker histone to chromatin is a key primary event in the reprogramming of somatic nuclei transplanted to amphibian oocytes.

show abstract

Reprogramming Factor Expression Initiates Widespread Targeted Chromatin Remodeling

Cited by 335 publications

References 23 publications

CHD1L Regulated PARP1-Driven Pluripotency and Chromatin Remodeling During the Early-Stage Cell Reprogramming

CHD1L Regulated PARP1-Driven Pluripotency and Chromatin Remodeling During the Early-Stage Cell Reprogramming

Mechanisms of nuclear reprogramming by eggs and oocytes: a deterministic process?

Reprogramming of gene expression following nuclear transfer to theXenopusoocyte

Contact Info

Product

Resources

About