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H4K16ac is dispensable for mammalian transcriptional control but necessary for a faithful genome duplication program [EdU-Huseq]

ABSTRACT: Histone acetylation has widely been assumed to directly instruct gene activation. Among acetylated residues, H4K16ac is one of the most abundant modifications, conserved across all eukaryotes. Despite its established role in X-chromosome hyperactivation in Drosophila, its function in mammalian cells has remained elusive. Here, we show that in human somatic cells, H4K16ac does not regulate gene expression, but instead controls the spatiotemporal program of genome duplication. By combining a meta-analysis of public datasets and perturbation experiments free of confounding effects, we found that H4K16ac is neither associated with nor required for transcriptional activity. Rather, H4K16ac depletion resulted in premature replication of heterochromatic regions and widespread alterations in replication timing across the genome. These defects were driven by the aberrant activation of cryptic replication origins at long terminal repeats (LTRs)—repetitive elements typically marked by H4K16ac and whose sequence context resembles that of canonical origins in euchromatic regions. Our findings reveal an unexpected role for one of the most prevalent chromatin modifications and uncover a new regulatory mechanism that ensures accurate genome duplication.

ORGANISM(S): Homo sapiens

PROVIDER: GSE286135 | GEO | 2025/08/19

REPOSITORIES: GEO

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H4K16ac is dispensable for mammalian transcriptional control but necessary for a faithful genome duplication program [REPLIseq]

Project description:Histone acetylation has widely been assumed to directly instruct gene activation. Among acetylated residues, H4K16ac is one of the most abundant modifications, conserved across all eukaryotes. Despite its established role in X-chromosome hyperactivation in Drosophila, its function in mammalian cells has remained elusive. Here, we show that in human somatic cells, H4K16ac does not regulate gene expression, but instead controls the spatiotemporal program of genome duplication. By combining a meta-analysis of public datasets and perturbation experiments free of confounding effects, we found that H4K16ac is neither associated with nor required for transcriptional activity. Rather, H4K16ac depletion resulted in premature replication of heterochromatic regions and widespread alterations in replication timing across the genome. These defects were driven by the aberrant activation of cryptic replication origins at long terminal repeats (LTRs)—repetitive elements typically marked by H4K16ac and whose sequence context resembles that of canonical origins in euchromatic regions. Our findings reveal an unexpected role for one of the most prevalent chromatin modifications and uncover a new regulatory mechanism that ensures accurate genome duplication.

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H4K16ac is dispensable for mammalian transcriptional control but necessary for a faithful genome duplication program [ChIP-seq]

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H4K16ac is dispensable for mammalian transcriptional control but necessary for a faithful genome duplication program [RNA-seq]

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H4K16ac is dispensable for mammalian transcriptional control but necessary for a faithful genome duplication program [EdU-Huseq]

Project description:H4K16ac is dispensable for mammalian transcriptional control but necessary for a faithful genome duplication program [EdU-Huseq]

| PRJNA1207990 | ENA

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Project description:modENCODE_submission_5260 This submission comes from a modENCODE project of Gary Karpen. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We aim to determine the locations of the major histone modifications across the Drosophila melanogaster genome. The modifications under study are involved in basic chromosomal functions such as DNA replication, gene expression, gene silencing, and inheritance. We will perform Chromatin ImmunoPrecipitation (ChIP) using the Illumina NGS sequencing platform. We will initially assay localizations using chromatin from three cell lines and two embryonic stages, and will then extend the analysis of a subset of proteins to four additional animal tissues/stages. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: Oregon-R(official name : Oregon-R-modENCODE genotype : wild type ); Developmental Stage: 3rd Instar Larvae; Genotype: wild type; EXPERIMENTAL FACTORS: Strain Oregon-R(official name : Oregon-R-modENCODE genotype : wild type ); Antibody H4K16ac(M) (target is H4K16ac); Developmental Stage 3rd Instar Larvae

2013-08-02 | E-GEOD-49497 | biostudies-arrayexpress

H4K16ac(M).OR Head Nuclei.Solexa

Project description:modENCODE_submission_5108 This submission comes from a modENCODE project of Gary Karpen. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We aim to determine the locations of the major histone modifications across the Drosophila melanogaster genome. The modifications under study are involved in basic chromosomal functions such as DNA replication, gene expression, gene silencing, and inheritance. We will perform Chromatin ImmunoPrecipitation (ChIP) using the Illumina NGS sequencing platform. We will initially assay localizations using chromatin from three cell lines and two embryonic stages, and will then extend the analysis of a subset of proteins to four additional animal tissues/stages. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: Oregon-R(official name : Oregon-R-modENCODE genotype : wild type ); Developmental Stage: Mixed Adult; Genotype: wild type; EXPERIMENTAL FACTORS: Strain Oregon-R(official name : Oregon-R-modENCODE genotype : wild type ); tissue (organism part) ; Antibody H4K16ac(M) (target is H4K16ac); Developmental Stage Mixed Adult

2013-05-28 | E-GEOD-47292 | biostudies-arrayexpress

H4K16ac(M).D.mel 3rd Instar Larvae Nuclei

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2011-10-12 | E-GEOD-32835 | biostudies-arrayexpress

H4K16ac(L).14-16 hr OR embryo

Project description:modENCODE_submission_3697 This submission comes from a modENCODE project of Gary Karpen. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We aim to determine the locations of the major histone modifications across the Drosophila melanogaster genome. The modifications under study are involved in basic chromosomal functions such as DNA replication, gene expression, gene silencing, and inheritance. We will perform Chromatin ImmunoPrecipitation (ChIP) using genomic tiling arrays. We will initially assay localizations using chromatin from three cell lines and two embryonic stages, and will then extend the analysis of a subset of proteins to four additional animal tissues/stages. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-chip. BIOLOGICAL SOURCE: Strain: Oregon-R(official name : Oregon-R-modENCODE genotype : wild type ); Developmental Stage: Embryo 14-16hr OR; Genotype: wild type; NUMBER OF REPLICATES: 4; EXPERIMENTAL FACTORS: Strain Oregon-R(official name : Oregon-R-modENCODE genotype : wild type ); Antibody H4K16ac(L) (target is H4K16ac); Developmental Stage Embryo 14-16hr OR

2013-02-22 | E-GEOD-44473 | biostudies-arrayexpress

H4K16ac(M).14-16 hr OR embryo

Project description:modENCODE_submission_3698 This submission comes from a modENCODE project of Gary Karpen. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We aim to determine the locations of the major histone modifications across the Drosophila melanogaster genome. The modifications under study are involved in basic chromosomal functions such as DNA replication, gene expression, gene silencing, and inheritance. We will perform Chromatin ImmunoPrecipitation (ChIP) using genomic tiling arrays. We will initially assay localizations using chromatin from three cell lines and two embryonic stages, and will then extend the analysis of a subset of proteins to four additional animal tissues/stages. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-chip. BIOLOGICAL SOURCE: Strain: Oregon-R(official name : Oregon-R-modENCODE genotype : wild type ); Developmental Stage: Embryo 14-16hr OR; Genotype: wild type; NUMBER OF REPLICATES: 4; EXPERIMENTAL FACTORS: Strain Oregon-R(official name : Oregon-R-modENCODE genotype : wild type ); Antibody H4K16ac(M) (target is H4K16ac); Developmental Stage Embryo 14-16hr OR

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