H3.3 contributes to chromatin accessibility and transcription factor binding at promoter-proximal regulatory elements in embryonic stem cells Article Swipe
Amanuel Tafessu
,
Ryan O’Hara
,
Sara Martire
,
Altair L. Dube
,
Purbita Saha
,
Vincent U. Gant
,
Laura A. Banaszynski
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1186/s13059-023-02867-3
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1186/s13059-023-02867-3
Background The histone variant H3.3 is enriched at active regulatory elements such as promoters and enhancers in mammalian genomes. These regions are highly accessible, creating an environment that is permissive to transcription factor binding and the recruitment of transcriptional coactivators that establish a unique chromatin post-translational landscape. How H3.3 contributes to the establishment and function of chromatin states at these regions is poorly understood. Results We perform genomic analyses of features associated with active promoter chromatin in mouse embryonic stem cells (ESCs) and find evidence of subtle yet widespread promoter dysregulation in the absence of H3.3. Loss of H3.3 results in reduced chromatin accessibility and transcription factor (TF) binding at promoters of expressed genes in ESCs. Likewise, enrichment of the transcriptional coactivator p300 and downstream histone H3 acetylation at lysine 27 (H3K27ac) is reduced at promoters in the absence of H3.3, along with reduced enrichment of the acetyl lysine reader BRD4. Despite the observed chromatin dysregulation, H3.3 KO ESCs maintain transcription from ESC-specific genes. However, upon undirected differentiation, H3.3 KO cells retain footprinting of ESC-specific TF motifs and fail to generate footprints of lineage-specific TF motifs, in line with their diminished capacity to differentiate. Conclusions H3.3 facilitates DNA accessibility, transcription factor binding, and histone post-translational modification at active promoters. While H3.3 is not required for maintaining transcription in ESCs, it does promote de novo transcription factor binding which may contribute to the dysregulation of cellular differentiation in the absence of H3.3.
Related Topics
Concepts
Biology
Embryonic stem cell
Chromatin
Transcription factor
Human genetics
Stem cell
Genetics
Cell biology
Computational biology
Promoter
ChIA-PET
Evolutionary biology
Gene
Chromatin remodeling
Gene expression
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1186/s13059-023-02867-3
- https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-023-02867-3
- OA Status
- gold
- Cited By
- 39
- References
- 87
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4320480622
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4320480622Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1186/s13059-023-02867-3Digital Object Identifier
- Title
-
H3.3 contributes to chromatin accessibility and transcription factor binding at promoter-proximal regulatory elements in embryonic stem cellsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-02-13Full publication date if available
- Authors
-
Amanuel Tafessu, Ryan O’Hara, Sara Martire, Altair L. Dube, Purbita Saha, Vincent U. Gant, Laura A. BanaszynskiList of authors in order
- Landing page
-
https://doi.org/10.1186/s13059-023-02867-3Publisher landing page
- PDF URL
-
https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-023-02867-3Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
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https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-023-02867-3Direct OA link when available
- Concepts
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Biology, Embryonic stem cell, Chromatin, Transcription factor, Human genetics, Stem cell, Genetics, Cell biology, Computational biology, Promoter, ChIA-PET, Evolutionary biology, Gene, Chromatin remodeling, Gene expressionTop concepts (fields/topics) attached by OpenAlex
- Cited by
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39Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 11, 2024: 20, 2023: 7, 2022: 1Per-year citation counts (last 5 years)
- References (count)
-
87Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.does | 221 |
| abstract_inverted_index.fail | 179 |
| abstract_inverted_index.find | 84 |
| abstract_inverted_index.from | 162 |
| abstract_inverted_index.line | 188 |
| abstract_inverted_index.novo | 224 |
| abstract_inverted_index.p300 | 123 |
| abstract_inverted_index.stem | 80 |
| abstract_inverted_index.such | 12 |
| abstract_inverted_index.that | 28, 41 |
| abstract_inverted_index.upon | 166 |
| abstract_inverted_index.with | 73, 143, 189 |
| abstract_inverted_index.BRD4. | 151 |
| abstract_inverted_index.ESCs, | 219 |
| abstract_inverted_index.ESCs. | 116 |
| abstract_inverted_index.H3.3, | 141 |
| abstract_inverted_index.H3.3. | 96, 241 |
| abstract_inverted_index.These | 20 |
| abstract_inverted_index.While | 210 |
| abstract_inverted_index.along | 142 |
| abstract_inverted_index.cells | 81, 171 |
| abstract_inverted_index.genes | 114 |
| abstract_inverted_index.mouse | 78 |
| abstract_inverted_index.their | 190 |
| abstract_inverted_index.these | 60 |
| abstract_inverted_index.which | 228 |
| abstract_inverted_index.(ESCs) | 82 |
| abstract_inverted_index.acetyl | 148 |
| abstract_inverted_index.active | 9, 74, 208 |
| abstract_inverted_index.factor | 33, 107, 201, 226 |
| abstract_inverted_index.genes. | 164 |
| abstract_inverted_index.highly | 23 |
| abstract_inverted_index.lysine | 130, 149 |
| abstract_inverted_index.motifs | 177 |
| abstract_inverted_index.poorly | 63 |
| abstract_inverted_index.reader | 150 |
| abstract_inverted_index.retain | 172 |
| abstract_inverted_index.states | 58 |
| abstract_inverted_index.subtle | 87 |
| abstract_inverted_index.unique | 44 |
| abstract_inverted_index.Despite | 152 |
| abstract_inverted_index.Results | 65 |
| abstract_inverted_index.absence | 94, 139, 239 |
| abstract_inverted_index.binding | 34, 109, 227 |
| abstract_inverted_index.genomic | 68 |
| abstract_inverted_index.histone | 3, 126, 204 |
| abstract_inverted_index.motifs, | 186 |
| abstract_inverted_index.perform | 67 |
| abstract_inverted_index.promote | 222 |
| abstract_inverted_index.reduced | 102, 134, 144 |
| abstract_inverted_index.regions | 21, 61 |
| abstract_inverted_index.results | 100 |
| abstract_inverted_index.variant | 4 |
| abstract_inverted_index.Abstract | 0 |
| abstract_inverted_index.However, | 165 |
| abstract_inverted_index.analyses | 69 |
| abstract_inverted_index.binding, | 202 |
| abstract_inverted_index.capacity | 192 |
| abstract_inverted_index.cellular | 235 |
| abstract_inverted_index.creating | 25 |
| abstract_inverted_index.elements | 11 |
| abstract_inverted_index.enriched | 7 |
| abstract_inverted_index.evidence | 85 |
| abstract_inverted_index.features | 71 |
| abstract_inverted_index.function | 55 |
| abstract_inverted_index.generate | 181 |
| abstract_inverted_index.genomes. | 19 |
| abstract_inverted_index.maintain | 160 |
| abstract_inverted_index.observed | 154 |
| abstract_inverted_index.promoter | 75, 90 |
| abstract_inverted_index.required | 214 |
| abstract_inverted_index.(H3K27ac) | 132 |
| abstract_inverted_index.Likewise, | 117 |
| abstract_inverted_index.chromatin | 45, 57, 76, 103, 155 |
| abstract_inverted_index.embryonic | 79 |
| abstract_inverted_index.enhancers | 16 |
| abstract_inverted_index.establish | 42 |
| abstract_inverted_index.expressed | 113 |
| abstract_inverted_index.mammalian | 18 |
| abstract_inverted_index.promoters | 14, 111, 136 |
| abstract_inverted_index.Background | 1 |
| abstract_inverted_index.associated | 72 |
| abstract_inverted_index.contribute | 230 |
| abstract_inverted_index.diminished | 191 |
| abstract_inverted_index.downstream | 125 |
| abstract_inverted_index.enrichment | 118, 145 |
| abstract_inverted_index.footprints | 182 |
| abstract_inverted_index.landscape. | 47 |
| abstract_inverted_index.permissive | 30 |
| abstract_inverted_index.promoters. | 209 |
| abstract_inverted_index.regulatory | 10 |
| abstract_inverted_index.undirected | 167 |
| abstract_inverted_index.widespread | 89 |
| abstract_inverted_index.Conclusions | 195 |
| abstract_inverted_index.accessible, | 24 |
| abstract_inverted_index.acetylation | 128 |
| abstract_inverted_index.coactivator | 122 |
| abstract_inverted_index.contributes | 50 |
| abstract_inverted_index.environment | 27 |
| abstract_inverted_index.facilitates | 197 |
| abstract_inverted_index.maintaining | 216 |
| abstract_inverted_index.recruitment | 37 |
| abstract_inverted_index.understood. | 64 |
| abstract_inverted_index.ESC-specific | 163, 175 |
| abstract_inverted_index.coactivators | 40 |
| abstract_inverted_index.footprinting | 173 |
| abstract_inverted_index.modification | 206 |
| abstract_inverted_index.accessibility | 104 |
| abstract_inverted_index.dysregulation | 91, 233 |
| abstract_inverted_index.establishment | 53 |
| abstract_inverted_index.transcription | 32, 106, 161, 200, 217, 225 |
| abstract_inverted_index.accessibility, | 199 |
| abstract_inverted_index.differentiate. | 194 |
| abstract_inverted_index.dysregulation, | 156 |
| abstract_inverted_index.differentiation | 236 |
| abstract_inverted_index.transcriptional | 39, 121 |
| abstract_inverted_index.differentiation, | 168 |
| abstract_inverted_index.lineage-specific | 184 |
| abstract_inverted_index.post-translational | 46, 205 |
| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 89 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 7 |
| citation_normalized_percentile.value | 0.9753127 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |