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Different Enhancer Classes in Drosophila Bind Different Architectural Proteins and Mediate Unique Chromatin Interactions and 3D Architecture

ABSTRACT: Different Enhancer Classes in Drosophila Bind Different Architectural Proteins and Mediate Unique Chromatin Interactions and 3D Architecture

PROVIDER: PRJNA319739 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3452730_1.fastq.gz	Fastqsanger.gz
	SRR3452730_2.fastq.gz	Fastqsanger.gz
	SRR3452740_1.fastq.gz	Fastqsanger.gz
	SRR3452740_2.fastq.gz	Fastqsanger.gz
	SRR3452731_1.fastq.gz	Fastqsanger.gz

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Different Enhancer Classes in Drosophila Bind Different Architectural Proteins and Mediate Unique Chromatin Interactions and 3D Architecture [ChIP-seq]

Project description:In this study, we further characterized the hkCP and dCP enhancers, which were identified by STARR-seq, and shown to have an intrinsic capacity to interact with a specific type of core promoter depending on the presence of a DRE motif [9]. hkCP enhancers are marked by H3K4me3, associated with TAD borders, and mediate large TSS-clustered interactions to promote robust transcription. Furthermore, they contain the architectural proteins CAP-H2, Chromator, DREF and Z4. In contrast, dCP enhancers are marked by H3K4me1, associated with chromatin loop anchors and are more commonly associated with single TSS-contacts. dCP enhancers are depleted of the hkCP-specific architectural proteins and show an enrichment for Fs(1)h-L and Rad21 instead. Thus, our data supports the model that the unique occupancy of architectural proteins in the distinct enhancer classes are key contributors to the types of interactions that enhancers can mediate genome-wide, ultimately affecting enhancer-promoter specificity.

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Different enhancer classes in Drosophila bind distinct architectural proteins and mediate unique chromatin interactions and 3D architecture.

Project description:Eukaryotic gene expression is regulated by enhancer-promoter interactions but the molecular mechanisms that govern specificity have remained elusive. Genome-wide studies utilizing STARR-seq identified two enhancer classes in Drosophila that interact with different core promoters: housekeeping enhancers (hkCP) and developmental enhancers (dCP). We hypothesized that the two enhancer classes are occupied by distinct architectural proteins, affecting their enhancer-promoter contacts. By evaluating ChIP-seq occupancy of architectural proteins, typical enhancer-associated proteins, and histone modifications, we determine that both enhancer classes are enriched for RNA Polymerase II, CBP, and architectural proteins but there are also distinctions. hkCP enhancers contain H3K4me3 and exclusively bind Cap-H2, Chromator, DREF and Z4, whereas dCP enhancers contain H3K4me1 and are more enriched for Rad21 and Fs(1)h-L. Additionally, we map the interactions of each enhancer class utilizing a Hi-C dataset with <1 kb resolution. Results suggest that hkCP enhancers are more likely to form multi-TSS interaction networks and be associated with topologically associating domain (TAD) borders, while dCP enhancers are more often bound to one or two TSSs and are enriched at chromatin loop anchors. The data support a model suggesting that the unique architectural protein occupancy within enhancers is one contributor to enhancer-promoter interaction specificity.

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Different Enhancer Classes in Drosophila Bind Different Architectural Proteins and Mediate Unique Chromatin Interactions and 3D Architecture

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