Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

GRO-seq analysis U1810 cells after 8h Rapamycin treatment and DMSO control

ABSTRACT: Investigating transcriptional changes after autophagy induction by rapamycin to compare changes in autophagy-related genes to changes in histone modifications.

INSTRUMENT(S): Illumina HiSeq 2000

ORGANISM(S): Homo sapiens

SUBMITTER: Jens Fuellgrabe

PROVIDER: E-MTAB-5490 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy.

Füllgrabe Jens J Lynch-Day Melinda A MA Heldring Nina N Li Wenbo W Struijk Robert B RB Ma Qi Q Hermanson Ola O Rosenfeld Michael G MG Klionsky Daniel J DJ Joseph Bertrand B

Nature 20130717 7463

Autophagy is an evolutionarily conserved catabolic process involved in several physiological and pathological processes. Although primarily cytoprotective, autophagy can also contribute to cell death; it is thus important to understand what distinguishes the life or death decision in autophagic cells. Here we report that induction of autophagy is coupled to reduction of histone H4 lysine 16 acetylation (H4K16ac) through downregulation of the histone acetyltransferase hMOF (also called KAT8 or MY ...[more]

PMID: 23863932

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Project description:Precise control of the innate immune response is required for resistance to microbial infections and maintenance of normal tissue homeostasis. Because this response involves coordinate regulation of hundreds of genes, it provides a powerful biological system to elucidate the molecular strategies that underlie signal- and time-dependent transitions of gene expression. Using a combination of genome-wide and gene-specific approaches, we provide evidence that rather than representing off/on transitions, Toll-like receptor 4 (TLR4)-dependent activation of nearly all immediate/early (I/E) and late response genes results from a sequential process in which signal-independent factors, exemplified by Gabpa, initially establish basal levels of gene expression that are then amplified by signal-dependent transcription factors. Promoters of I/E genes are distinguished from those of late genes by the use of distinct sets of signal-dependent transcription factors, preferential binding of TBP and basal enrichment for RNA Pol II immediately downstream of transcriptional start sites. Global nuclear run-on (GRO) sequencing and total RNA sequencing further indicates that TLR4 signaling markedly increases efficiency of transcriptional elongation of nearly all I/E genes, while RNA splicing is largely unaffected. NCoR/SMRT co-repressor complexes are unexpectedly found to be associated with H3K4me3-positive promoters of TLR4-responsive genes that exhibit a broad range of basal expression levels, implying a dynamic, rather than static role in regulation of gene expression. Collectively, these findings reveal mechanisms underlying temporally distinct patterns of TLR4-dependent gene activation required for homeostasis and effective immune responses. ChIP-Seq, Total RNA-Seq, Gro-Seq, and gene expression profiling was performed in macrophages treated with Kdo2 Lipid A. Control samples for H3K4me3 in Macrophages and B cells, in addition to control microarray data are included in GEO accession# GSE21512. FASTA files are available for older experiments that lack quality read information (i.e. no FASTQ file)

Dataset Information

GRO-seq analysis U1810 cells after 8h Rapamycin treatment and DMSO control

Publications

The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy.

Similar Datasets

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