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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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A functional genomics approach identifies the GATA factor SERPENT as a tissue-specific partner of CLOCK/CYCLE in the Drosophila circadian clock

ABSTRACT: Broadly expressed transcriptions factors (TFs) control tissue-specific programs of gene expression through interactions with local TF networks. Prime examples are the circadian clock TFs CLOCK (CLK) and CYCLE (CYC or BMAL1): while they control a core transcriptional circuit throughout animal bodies, downstream clock target genes and circadian physiology are tissue-specific. Here, we use ChIP-seq to determine the regulatory targets of Drosophila CLK and CYC, which we epitope-tagged by homologous recombination. Both TFs have distinct binding sites in heads versus bodies, suggesting that they directly control tissue-specific downstream target genes. Analysis of these context-specific binding sites revealed distinct sequence motifs for putative clock partner factors, including a motif for the GATA factor SERPENT (SRP). SRP indeed synergistically enhances CLK/CYC-mediated activity of a cis-regulatory region bound by CLK/CYC specifically in bodies. These results reveal how universal clock circuits can generate tissue-specific outputs and demonstrate an approach to dissect regulatory interactions more generally. We sequenced ChIP and input samples, as well as M-bM-^@M-^\mockM-bM-^@M-^] samples for which we performed ChIP with the V5 antibody from wildtype w- flies (not carrying the V5 tag) for two independent biological replicates each, summing to 24 libraries in total.

ORGANISM(S): Drosophila melanogaster

SUBMITTER: Anais Bardet

PROVIDER: E-GEOD-40467 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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CLOCKWORK ORANGE promotes CLOCK-CYCLE activation via the Drosophila ortholog of CLOCK INTERACING PROTEIN, CIRCADIAN (ChIP-Seq)

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2021-07-23 | GSE165042 | GEO

CLOCKWORK ORANGE promotes CLOCK-CYCLE activation via the Drosophila ortholog of CLOCK INTERACING PROTEIN, CIRCADIAN (RNA-Seq)

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2021-07-23 | GSE165043 | GEO

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2013-05-03 | E-GEOD-46576 | biostudies-arrayexpress

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cis-Regulatory Requirements for Tissue-Specific Programs of the Circadian Clock

2013-06-01 | GSE40467 | GEO

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The transcription factor Mef2 links the Drosophila core clock to Fas2, neuronal morphology and circadian behavior

2013-05-03 | GSE46576 | GEO

CLK:BMAL1 is a pioneer-like transcription factor [CLK_ChIP]

Project description:The mammalian circadian clock relies on the master genes CLOCK (CLK) and BMAL1 and drives rhythmic gene expression to regulate biological functions under circadian control. We recently uncovered a surprising disconnect between the rhythmic binding of CLK:BMAL1 on DNA and the transcription of its target genes, suggesting that they are regulated by as yet uncharacterized mechanisms. Here we show that rhythmic CLK:BMAL1 DNA binding promotes rhythmic chromatin opening. The underlying mechanisms include CLK:BMAL1 binding to nucleosomes and rhythmic chromatin modifications, including the incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLK:BMAL1, suggesting that the activity and the tissue-specific expression of these other transcription factors contribute to the genome-wide CLK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation, well beyond the current confines of developmental/cell specification. Mouse liver CLK ChIP-Seq signal on Mnase-digested or sonicated chromatin, at 2 different time point (ZT22 and ZT06) from the same mice. Libraries were sequenced using Ilumina HiSeq2000. For Mnase-digested chromatin, libraries contained a mononucleosome insert (e.g., ~147bp), whereas the insert was ~150-300bp for sonicated chromatin.

2014-01-06 | E-GEOD-47144 | biostudies-arrayexpress

CLK:BMAL1 is a pioneer-like transcription factor [H2AZ-ChIP]

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2014-01-06 | E-GEOD-47143 | biostudies-arrayexpress

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Project description:The mammalian circadian clock relies on the master genes CLOCK (CLK) and BMAL1 and drives rhythmic gene expression to regulate biological functions under circadian control. We recently uncovered a surprising disconnect between the rhythmic binding of CLK:BMAL1 on DNA and the transcription of its target genes, suggesting that they are regulated by as yet uncharacterized mechanisms. Here we show that rhythmic CLK:BMAL1 DNA binding promotes rhythmic chromatin opening. The underlying mechanisms include CLK:BMAL1 binding to nucleosomes and rhythmic chromatin modifications, including the incorporation of the histone variant H2A.Z. This rhythmic chromatin remodeling mediates the rhythmic binding of other transcription factors adjacent to CLK:BMAL1, suggesting that the activity and the tissue-specific expression of these other transcription factors contribute to the genome-wide CLK:BMAL1 heterogeneous transcriptional output. These data therefore indicate that the clock regulation of transcription relies on the rhythmic regulation of chromatin accessibility and suggest that the concept of pioneer function extends to acute gene regulation, well beyond the current confines of developmental/cell specification. Mouse liver nucleosome profile assayed by MNase-Seq over 6 time points of the 24h light:dark cycle (4 wild-type and 4 Bmal1-/- mice per time point). Illumina libraries containing a mononucleosome insert were sequenced using Ilumina HiSeq2000.

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