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The role of HNRNPU and the nuclear matrix in human pluripotent stem cells [CUT&Tag]

ABSTRACT: The role of HNRNPU and the nuclear matrix in human pluripotent stem cells [CUT&Tag]

PROVIDER: PRJNA1013377 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25918244_1.fastq.gz	Fastqsanger.gz
	SRR25918244_2.fastq.gz	Fastqsanger.gz
	SRR25918245_1.fastq.gz	Fastqsanger.gz
	SRR25918245_2.fastq.gz	Fastqsanger.gz
	SRR25918246_1.fastq.gz	Fastqsanger.gz

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The role of HNRNPU and the nuclear matrix in human pluripotent stem cells [CUT&Tag]

Project description:During early embryogenesis the fertilized zygote proceeds through an intricate developmental program, accompanyed by DNA and chromatin remodelling. However, the mechanisms governing this reconfiguring are poorly understood. Parts of the embryogenesis developmental program can be captured in vitro in the form of two types of human pluripotent stem cells (hPSC): naïve and primed hPSCs. Naïve hPSCs resemble the inner cell mass of the blastocyst, whilst primed hPSCs resemble the post-implantation embryo. The nucleus is made of DNA wrapped around chromatin, and the nuclear matrix, a proteinaceous gel that provides structure. Here, we show that disruptions in the nuclear matrix caused primed hPSCs to spontaneously convert to the naïve, earlier embryonic state.

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The nuclear matrix associating protein HNRNPU functions as a key regulator of 3D genome architecture [ChIP-Seq 2]

Project description:Here we show that HNRNPU, the major nuclear matrix attachment factor, is necessary to maintain proper nuclear architecture in mouse hepatocytes. Upon HNRNPU depletion, the interactions between chromatin and nuclear lamina have been changed dramatically；chromatin organization is globally changed; boundaries of topologically associating domains (TADs) become weaker; inter-TAD interactions are increased; thousands of genes are significantly altered coincident with 3D chromatin changes. Mechanically, HNRNPU interacts with CTCF and RAD21, which affects the binding of RAD21 to the chromatin significantly, whereas CTCF bindings are almost unchanged, what’ more, the decrease of binding strengths are highly correlated with the weakness of loop bounded by Rad21. Taken together, we identify HNRNPU as a key regulator of chromatin architecture, and our data suggest the importance of nuclear matrix associating factors in 3D genome organization.

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Project description:Higher-order chromatin conformation plays critical role in regulating gene expression and biological development, here we show that HNRNPU, a nuclear matrix attachment factor, is a regulator of 3D genome architecture at multiple levels in mouse hepatocytes. We demonstrate that depletion of HNRNPU results into a global reorganization of nuclear bodies and re-localization of chromatin towards nuclear periphery. Additionally, upon HNRNPU depletion, chromatin interactions between A-type (active) and B-type (inactive) compartments increase significantly but those among same types of compartments decrease significantly, which associate with global gene expression changes. While TADs remain largely invariant, both inter- and intra-TAD interactions increase significantly in A-type compartments but decrease in B-type compartments. Mechanically, HNRNPU complexes with structural proteins CTCF and RAD21; depletion of HNRNPU specifically weakens the bindings of RAD21 to the chromatin, which is highly correlated with the weakness of chromatin loops.

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