Search bioRxivSearch

Biology subjects

Paul Bertone

Publications and source records attributed to Paul Bertone.

2 recordsLinked to original sources

Mbd3 and deterministic reprogramming

Embryonic development requires the activity of the Nucleosome Remodeling and Deacetylase (NuRD) complex. NuRD functionality can be ablated by rendering cells devoid of methyl-CpG-binding domain protein 3 (Mbd3), a critical component that confers stability to the complex1. Previous studies noted that Mbd3-/- embryonic stem (ES) cells misregulate a subset of pluripotency-associated genes, and subsequently fail to engage in cell differentiation into embryonic lineages when self-renewal requisites (e.g. LIF) are withdrawn from culture media2-3. Components of the NuRD complex have been shown to interact with Oct4 and Nanog, two important transcription factors operative in the production of iPS cells4-7. Thus, elucidating the role of Mbd3/NuRD in the reprogramming process is of relevance to the field.\n\nRais et al. reported the remarkable obse ...

Cell Biology

Neural lineage induction reveals multi-scale dynamics of 3D chromatin organization

Regulation of gene expression underlies cell identity. Chromatin structure and gene activity are linked at multiple levels, via positioning of genomic loci to transcriptionally permissive or repressive environments and by connecting cis-regulatory elements such as promoters and enhancers. However, the genome-wide dynamics of these processes during cell differentiation has not been characterized. Using tethered chromatin conformation capture (TCC) sequencing we determined global three-dimensional chromatin structures in mouse embryonic stem (ES) and neural stem (NS) cell derivatives. We found that changes in the propensity of genomic regions to form inter-chromosomal contacts are pervasive in neural induction and are associated with the regulation of gene expression. Moreover, we found a pronounced contribution of euchromatic domains to the intra-chromosomal interaction network of pluripotent cells, indicating the existence of an ES cell-specific mode of chromatin organization. Mapping of promoter-enhancer interactions in pluripotent and differentiated cells revealed that spatial proximity without enhancer element activity is a common architectural feature in cells undergoing early developmental changes. Activity-independent formation of higher-order contacts between cis-regulatory elements, predominant at complex loci, may thus provide an additional layer of transcriptional control.

Molecular Biology