Showing papers by "Julia Zeitlinger published in 2017"
TL;DR: Using the recently developed ChIP-nexus method, it is found that Pol II pausing inhibits new initiation and proposed that paused Pol II helps prevent new initiation between transcription bursts, which may reduce noise.
Abstract: RNA polymerase II (Pol II) pauses downstream of the transcription initiation site before beginning productive elongation This pause is a key component of metazoan gene expression regulation Some promoters have a strong disposition for Pol II pausing and often mediate faster, more synchronous changes in expression This requires multiple rounds of transcription and thus cannot rely solely on pause release However, it is unclear how pausing affects the initiation of new transcripts during consecutive rounds of transcription Using our recently developed ChIP-nexus method, we find that Pol II pausing inhibits new initiation We propose that paused Pol II helps prevent new initiation between transcription bursts, which may reduce noise
203 citations
TL;DR: Analysis of enhancers during dorsal-ventral axis formation in the Drosophila embryo finds that the poised enhancer signature is specifically generated during patterning in the tissue where the enhancers are not induced, including at enhancers that are known to be repressed by a transcriptional repressor.
Abstract: Histone modifications are frequently used as markers for enhancer states, but how to interpret enhancer states in the context of embryonic development is not clear. The poised enhancer signature, involving H3K4me1 and low levels of H3K27ac, has been reported to mark inactive enhancers that are poised for future activation. However, future activation is not always observed, and alternative reasons for the widespread occurrence of this enhancer signature have not been investigated. By analyzing enhancers during dorsal-ventral (DV) axis formation in the Drosophila embryo, we find that the poised enhancer signature is specifically generated during patterning in the tissue where the enhancers are not induced, including at enhancers that are known to be repressed by a transcriptional repressor. These results suggest that, rather than serving exclusively as an intermediate step before future activation, the poised enhancer state may be a mark for spatial regulation during tissue patterning. We discuss the possibility that the poised enhancer state is more generally the result of repression by transcriptional repressors.
47 citations
TL;DR: Analysis of putative target genes indicates that Hoxa1 has input to components of major signaling pathways, including Wnt, TGF-β, Hedgehog and Hippo, and frequently does so by targeting multiple components of a pathway such as secreted inhibitors, ligands, receptors and down-stream components.
42 citations
TL;DR: Using ChIP-nexus, Hippo signaling is found to keep Ras targets in check by directly regulating the expression of two key downstream transcription factors of Ras signaling: the ETS-domain transcription factor Pointed and the repressor Capicua.
36 citations
TL;DR: Extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes are discovered, indicating that the specificity of HOXA1 during development may be regulated though a complex cross-Regulatory network of HOxA1 andTALE proteins.
Abstract: Hoxa1 has diverse functional roles in differentiation and development. We identify and characterize properties of regions bound by HOXA1 on a genome-wide basis in differentiating mouse ES cells. HOXA1-bound regions are enriched for clusters of consensus binding motifs for HOX, PBX, and MEIS, and many display co-occupancy of PBX and MEIS. PBX and MEIS are members of the TALE family and genome-wide analysis of multiple TALE members (PBX, MEIS, TGIF, PREP1, and PREP2) shows that nearly all HOXA1 targets display occupancy of one or more TALE members. The combinatorial binding patterns of TALE proteins define distinct classes of HOXA1 targets, which may create functional diversity. Transgenic reporter assays in zebrafish confirm enhancer activities for many HOXA1-bound regions and the importance of HOX-PBX and TGIF motifs for their regulation. Proteomic analyses show that HOXA1 physically interacts on chromatin with PBX, MEIS, and PREP family members, but not with TGIF, suggesting that TGIF may have an independent input into HOXA1-bound regions. Therefore, TALE proteins appear to represent a wide repertoire of HOX cofactors, which may coregulate enhancers through distinct mechanisms. We also discover extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes, indicating that the specificity of HOXA1 during development may be regulated though a complex cross-regulatory network of HOXA1 and TALE proteins. This study provides new insight into a regulatory network involving combinatorial interactions between HOXA1 and TALE proteins.
35 citations