Dataset Information

Domain model explains propagation dynamics and stability of K27 and K36 methylation landscape

ABSTRACT: Chromatin states must be stably maintained during cell proliferation to uphold cellular identity and genome integrity. Inheritance of histone modifications across cell division is thought to be central in this process. However, the histone modification landscape is challenged by the incorporation of new unmodified histones during each cell cycle and the principles that govern heritability remain poorly defined. Here, we take a quantitative approach and develop a reusable computational model that describes propagation of K27 and K36 methylation states. We measure combinatorial K27 and K36 methylation patterns by quantitative mass spectrometry on subsequent generations of histones in the presence and absence of enzymatic inhibition. Our modelling rejects active global demethylation and invoke the existence of 8 domains defined by distinct methylation endpoints. We find that K27me3 on pre- existing histones stimulates the rate of de novo K27me3 establishment, supporting a read-write mechanism in timely chromatin restoration. Finally, we provide a detailed, quantitative picture of the mutual antagonism between K27 and K37 methylation, and propose that this antagonism enhance the stability of epigenetic states across cell division.

OTHER RELATED OMICS DATASETS IN: GSE135029

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Embryonic Stem Cell

SUBMITTER: Moritz Voelker-Albert

LAB HEAD: Prof. Dr. Axel Imhof

PROVIDER: PXD014807 | Pride | 2020-01-29

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	H3_41-49_all_160419.xlsx	Xlsx
	PeptideRatioResults_H3_27-40_CAL311-313_280918.xlsx	Xlsx
	PeptideRatioResults_H3_27-40_CAL314-316_280918.xlsx	Xlsx
	PeptideRatioResults_H3_27-40_CAL317-319_280918.xlsx	Xlsx
	PeptideRatioResults_H3_27-40_K27M_071217_ordered.xlsx	Xlsx

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Publications

Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes.

Alabert Constance C Loos Carolin C Voelker-Albert Moritz M Graziano Simona S Forné Ignasi I Reveron-Gomez Nazaret N Schuh Lea L Hasenauer Jan J Marr Carsten C Imhof Axel A Groth Anja A

Cell reports 20200101 4

Chromatin states must be maintained during cell proliferation to uphold cellular identity and genome integrity. Inheritance of histone modifications is central in this process. However, the histone modification landscape is challenged by incorporation of new unmodified histones during each cell cycle, and the principles governing heritability remain unclear. We take a quantitative computational modeling approach to describe propagation of histone H3K27 and H3K36 methylation states. We measure co ...[more]

PMID: 31995760

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