Laurent M. Sachs

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Spatial genome organization and its effect on transcription remains a fundamental question. We applied an advanced chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) strategy to comprehensively map higher-order chromosome folding and specific chromatin interactions mediated by CCCTC-binding factor (CTCF) and RNA polymerase II (RNAPII)(More)
Nuclear receptors (NRs) are transcription factors that are implicated in several biological processes such as embryonic development, homeostasis, and metabolic diseases. To study the role of NRs in development, it is critically important to know when and where individual genes are expressed. Although systematic expression studies using reverse transcriptase(More)
Transcriptional activation from chromatin by nuclear receptors (NRs) requires multiple cofactors including CBP/p300, SWI/SNF and Mediator. How NRs recruit these multiple cofactors is not clear. Here we show that activation by androgen receptor and thyroid hormone receptor is associated with the promoter targeting of SRC family members, p300, SWI/SNF and the(More)
Amphibian metamorphosis is marked by dramatic, thyroid hormone (TH)-induced changes involving gene regulation by TH receptor (TR). It has been postulated that TR-mediated gene regulation involves chromatin remodeling. In the absence of ligand, TR can repress gene expression by recruiting a histone deacetylase complex, whereas liganded TR recruits a histone(More)
N-CoR (nuclear receptor corepressor) is a corepressor for multiple transcription factors including unliganded thyroid hormone receptors (TRs). In vitro, N-CoR can interact with the Sin3 corepressor, which in turn binds to the histone deacetylase Rpd3 (HDAC1), predicting the existence of a corepressor complex containing N-CoR, Sin3, and histone deacetylase.(More)
The diversity of thyroid hormone T(3) effects in vivo makes their molecular analysis particularly challenging. Indeed, the current model of the action of T(3) and its receptors on transcription does not reflect this diversity. Here, T(3)-dependent amphibian metamorphosis was exploited to investigate, in an in vivo developmental context, how T(3) directly(More)
Metamorphosis in amphibians is marked by dramatic thyroid hormone-induced changes that include tail regression. To examine thyroid hormone effects on gene transcription during the early stages of tail resorption, we injected exogenous genes directly into the caudal skeletal muscle of Xenopus tadpoles and followed their expression in vivo. Gene expression(More)
Thyroid hormone receptors generally activate transcription of target genes in the presence of thyroid hormone (T(3)) and repress their transcription in its absence. Here, we investigated the role of unliganded thyroid hormone receptor (TR) during vertebrate development using an amphibian model. Previous studies led to the hypothesis that before production(More)
There is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate that binding of TH T3 (triiodothyronine) to THRB induces senescence and deoxyribonucleic acid (DNA) damage in cultured cells and in tissues of young hyperthyroid mice. T3 induces a rapid(More)
Thyroid hormone (TH) plays a causative role in anuran metamorphosis. This effect is presumed to be manifested through the regulation of gene expression by TH receptors (TRs). TRs can act as both activators and repressors of a TH-inducible gene depending upon the presence and absence of TH, respectively. We have been investigating the roles of TRs during(More)