Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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HSF1 regulates transcription of sex-chromosomal multicopy genes during post-meiotic repression

ABSTRACT: Mapping of in vivo targets for HSF1 by using mammalian tissue material in a global ChIP-chip promoter screen. Chromatin was isolated from three wild-type (WT) mouse testes, crosslinked and sonicated into fragments of 100-500 bp, and the quality of the DNA was controlled before the immunoprecipitation, showing no signs of degradation. The DNA amplified from the HSF1 immunoprecipitation samples was labeled and hybridized against the total input DNA samples, on a 1.5 kb promoter tiling array (NimbleGen Systems Inc.), covering ~26000 promoters of the mouse genome. After hybridization and scanning, HSF1 hybridization signals were Lowess normalized to produce log2 ratios (HSF1 ChIP/Input DNA) for all replicate arrays. The promoter values were calculated as average log2 ratios over all probes for each promoter. To identify the HSF1 target population, we used a non-arbitrary analysis method called RankProd described in Breitling et al. 2004. RankProd has been published as an R/Bioconductor package. HSF1 ChIP sample vs. Input sample (reference), biological replicates: 3, one replicate per array.

ORGANISM(S): Mus musculus

SUBMITTER: Lea Sistonen

PROVIDER: E-GEOD-22492 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Heat shock transcription factor 1 localizes to sex chromatin during meiotic repression.

Akerfelt Malin M Vihervaara Anniina A Laiho Asta A Conter Annie A Christians Elisabeth S ES Sistonen Lea L Henriksson Eva E

The Journal of biological chemistry 20100827 45

Heat shock factor 1 (HSF1) is an important transcription factor in cellular stress responses, cancer, aging, and developmental processes including gametogenesis. Disruption of Hsf1, together with another HSF family member, Hsf2, causes male sterility and complete lack of mature sperm in mice, but the specific role of HSF1 in spermatogenesis has remained unclear. Here, we show that HSF1 is transiently expressed in meiotic spermatocytes and haploid round spermatids in mouse testis. The Hsf1(-/-) m ...[more]

PMID: 20802198

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Project description:Heat shock response (HSR) is critical for survival of organisms undergoing proteotoxic stress. Heat shock factor 1 (HSF1) is widely believed to be the master regulator of this response. Here, we examined the kinetics of the transcriptional response and HSF1 binding changes genome-wide after heat shock (HS) with high sensitivity and high spatial and temporal resolution using PRO-seq and ChIP-seq assays respectively in wild type and in hsf1-deletion mouse embryonic fibroblasts. The transcriptional response is rapid, dynamic, and extensive with activation of several hundred genes and repression of several thousands of genes. Although HSF1 is critically required for classical inducible Heat Shock Protein (HSP) genes, it is not required for the majority of gene activation. HSF1 acts mechanistically to promote RNA polymerase II (Pol II) release from the promoter-proximal pause, while recruitment and initiation of Pol II are predominantly HSF1-independent. Surprisingly, a major class of cytoskeleton genes is immediately (within 2.5 minutes) and transiently activated in an HSF1-independent manner. A second wave of regulation is characterized by robust activation or repression of new sets of genes. The broad repression of thousands of genes, a quarter of which are repressed immediately upon HS and the rest are repressed in the second wave of regulation, is mediated at the level of decreasing Pol II pause release and not at prior steps of Pol II recruitment or initiation. Notably, heat shock does not induce transcription of some previously defined HSP genes, and HSF2 â a homolog of HSF1 â does not compensate for the lack of HSF1. Together, these findings indicate that mammalian cells cope with stress by rapidly inducing pervasive and dramatic changes in transcription that are largely modulated at the step of pause release, and only a fraction of this regulation is HSF1-dependent. Examination of transcriptional regulation before and after heat shock in WT, HSF1-/-, and HSF1&2-/- MEFs

Dataset Information

HSF1 regulates transcription of sex-chromosomal multicopy genes during post-meiotic repression

Publications

Heat shock transcription factor 1 localizes to sex chromatin during meiotic repression.

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