Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

KRAB/KAP1-microRNA cascade regulates erythropoiesis through the stage-specific control of mitophagy [Seq]

ABSTRACT: A multilayered transcription regulatory system is unveiled, where protein- and RNA-based repressors are super-imposed in combinatorial fashion to govern the timely triggering of an essential step of erythropoiesis Analyses of transcriptional profiles and chromatin state in KAP1 WT and KO (or KD) cells

ORGANISM(S): Homo sapiens

SUBMITTER: Adamandia Kapopoulou

PROVIDER: E-GEOD-44061 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy.

Barde Isabelle I Rauwel Benjamin B Marin-Florez Ray Marcel RM Corsinotti Andrea A Laurenti Elisa E Verp Sonia S Offner Sandra S Marquis Julien J Kapopoulou Adamandia A Vanicek Jiri J Trono Didier D

Science (New York, N.Y.) 20130314 6130

During hematopoiesis, lineage- and stage-specific transcription factors work in concert with chromatin modifiers to direct the differentiation of all blood cells. We explored the role of KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor KAP1 in this process. In mice, hematopoietic-restricted deletion of Kap1 resulted in severe hypoproliferative anemia. Kap1-deleted erythroblasts failed to induce mitophagy-associated genes and retained mitochondria. This was due to persistent ex ...[more]

PMID: 23493425

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Project description:Over the past decade, genome-wide assays have underscored the broad sweep of circadian gene expression. A substantial fraction of the transcriptome undergoes oscillations in many organisms and tissues, which governs the many biochemical, physiological and behavioral functions under circadian control. Based predominantly on the transcription feedback loops important for core circadian timekeeping, it is commonly assumed that this widespread mRNA cycling reflects circadian transcriptional cycling. To address this issue, we directly measured dynamic changes in mouse liver transcription using Nascent-Seq. Many genes are rhythmically transcribed over the 24h day, which include precursors of several non-coding RNAs as well as the expected set of core clock genes. Surprisingly however, nascent RNA rhythms overlap poorly with mRNA abundance rhythms assayed by RNA-seq. This is because most mouse liver genes with rhythmic mRNA expression manifest poor transcriptional rhythms, indicating a prominent role of post-transcriptional regulation in setting mRNA cycling amplitude. To gain further insight into circadian transcriptional regulation, we also characterized the rhythmic transcription of liver genes targeted by the transcription factors CLOCK and BMAL1; they directly target other core clock genes and sit at the top of the molecular circadian clock hierarchy in mammals. CLK:BMAL1 rhythmically bind at the same discrete phase of the circadian cycle to all target genes, which not surprisingly have a much higher percentage of rhythmic transcription than the genome as a whole. However, there is a surprisingly heterogeneous set of cycling transcription phases of direct target genes, which even include core clock genes. This indicates a disconnect between rhythmic DNA binding and the peak of transcription, which is likely due to other transcription factors that collaborate with CLK:BMAL1. In summary, the application of Nascent-Seq to a mammalian tissue provides surprising insights into the rhythmic control of gene expression and should have broad applications beyond the analysis of circadian rhythms. CLK and BMAL1 DNA binding profile in the mouse liver at ZT8, sequenced along an Input sample using GAII (ChIP-Seq) Supplementary file ChIPSeq_Mouse_Liver_Processed_data_Table1.txt represents annotated CLK and BMAL1 peaks.

Dataset Information

KRAB/KAP1-microRNA cascade regulates erythropoiesis through the stage-specific control of mitophagy [Seq]

Publications

A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy.

Similar Datasets

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