Chromatin States Reveal Functional Associations for Globally Defined Transcription Start Sites in Four Human Cell Lines

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2014 Mar 28

PMID 24669905

Citations 7

Authors

Morten Rye

Geir Kjetil Sandve

Carsten O Daub

Hideya Kawaji

Piero Carninci

Alistair R R Forrest

Finn Drablos

Affiliations

Soon will be listed here.

Abstract

Background: Deciphering the most common modes by which chromatin regulates transcription, and how this is related to cellular status and processes is an important task for improving our understanding of human cellular biology. The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome. Here we investigate chromatin features around a comprehensive set of transcription start sites in four cell lines by integrating data from these two projects.

Results: Transcription start sites can be distinguished by chromatin states defined by specific combinations of both chromatin mark enrichment and the profile shapes of these chromatin marks. The observed patterns can be associated with cellular functions and processes, and they also show association with expression level, location relative to nearby genes, and CpG content. In particular we find a substantial number of repressed inter- and intra-genic transcription start sites enriched for active chromatin marks and Pol II, and these sites are strongly associated with immediate-early response processes and cell signaling. Associations between start sites with similar chromatin patterns are validated by significant correlations in their global expression profiles.

Conclusions: The results confirm the link between chromatin state and cellular function for expressed transcripts, and also indicate that active chromatin states at repressed transcripts may poise transcripts for rapid activation during immune response.

Citing Articles

Dose rate dependent reduction in chromatin accessibility at transcriptional start sites long time after exposure to gamma radiation.

Dahl H, Ballangby J, Tengs T, Wojewodzic M, Eide D, Brede D Epigenetics. 2023; 18(1):2193936.

PMID: 36972203 PMC: 10054331. DOI: 10.1080/15592294.2023.2193936.

Prediction of Rice Transcription Start Sites Using TransPrise: A Novel Machine Learning Approach.

Pachganov S, Murtazalieva K, Zarubin A, Taran T, Chartier D, Tatarinova T Methods Mol Biol. 2021; 2238:261-274.

PMID: 33471337 DOI: 10.1007/978-1-0716-1068-8_17.

Acute Stress Induces Cognitive Improvement in the Novel Object Recognition Task by Transiently Modulating Bdnf in the Prefrontal Cortex of Male Rats.

Brivio P, Sbrini G, Riva M, Calabrese F Cell Mol Neurobiol. 2020; 40(6):1037-1047.

PMID: 31960229 PMC: 11448843. DOI: 10.1007/s10571-020-00793-7.

TransPrise: a novel machine learning approach for eukaryotic promoter prediction.

Pachganov S, Murtazalieva K, Zarubin A, Sokolov D, Chartier D, Tatarinova T PeerJ. 2019; 7:e7990.

PMID: 31695967 PMC: 6827441. DOI: 10.7717/peerj.7990.

The role of the genome in experience-dependent plasticity: Extending the analogy of the genomic action potential.

Clayton D, Anreiter I, Aristizabal M, Frankland P, Binder E, Citri A Proc Natl Acad Sci U S A. 2019; 117(38):23252-23260.

PMID: 31127037 PMC: 7519304. DOI: 10.1073/pnas.1820837116.

References

Orom U, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G . Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010; 143(1):46-58. PMC: 4108080. DOI: 10.1016/j.cell.2010.09.001. View

Kanamori-Katayama M, Itoh M, Kawaji H, Lassmann T, Katayama S, Kojima M . Unamplified cap analysis of gene expression on a single-molecule sequencer. Genome Res. 2011; 21(7):1150-9. PMC: 3129257. DOI: 10.1101/gr.115469.110. View

Wasserman N, Aneas I, Nobrega M . An 8q24 gene desert variant associated with prostate cancer risk confers differential in vivo activity to a MYC enhancer. Genome Res. 2010; 20(9):1191-7. PMC: 2928497. DOI: 10.1101/gr.105361.110. View

Li G, Ruan X, Auerbach R, Sandhu K, Zheng M, Wang P . Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell. 2012; 148(1-2):84-98. PMC: 3339270. DOI: 10.1016/j.cell.2011.12.014. View

Ernst J, Kheradpour P, Mikkelsen T, Shoresh N, Ward L, Epstein C . Mapping and analysis of chromatin state dynamics in nine human cell types. Nature. 2011; 473(7345):43-9. PMC: 3088773. DOI: 10.1038/nature09906. View

Li B, Carey M, Workman J . The role of chromatin during transcription. Cell. 2007; 128(4):707-19. DOI: 10.1016/j.cell.2007.01.015. View

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

Lim P, Hardy K, Bunting K, Ma L, Peng K, Chen X . Defining the chromatin signature of inducible genes in T cells. Genome Biol. 2009; 10(10):R107. PMC: 2784322. DOI: 10.1186/gb-2009-10-10-r107. View

Bertilsson H, Tessem M, Flatberg A, Viset T, Gribbestad I, Angelsen A . Changes in gene transcription underlying the aberrant citrate and choline metabolism in human prostate cancer samples. Clin Cancer Res. 2012; 18(12):3261-9. DOI: 10.1158/1078-0432.CCR-11-2929. View

10.

Bulger M, Groudine M . Functional and mechanistic diversity of distal transcription enhancers. Cell. 2011; 144(3):327-39. PMC: 3742076. DOI: 10.1016/j.cell.2011.01.024. View

11.

Visser M, Kayser M, Palstra R . HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. Genome Res. 2012; 22(3):446-55. PMC: 3290780. DOI: 10.1101/gr.128652.111. View

12.

Cabili M, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A . Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 2011; 25(18):1915-27. PMC: 3185964. DOI: 10.1101/gad.17446611. View

13.

Barski A, Jothi R, Cuddapah S, Cui K, Roh T, Schones D . Chromatin poises miRNA- and protein-coding genes for expression. Genome Res. 2009; 19(10):1742-51. PMC: 2765269. DOI: 10.1101/gr.090951.109. View

14.

John S, Sabo P, Thurman R, Sung M, Biddie S, Johnson T . Chromatin accessibility pre-determines glucocorticoid receptor binding patterns. Nat Genet. 2011; 43(3):264-8. PMC: 6386452. DOI: 10.1038/ng.759. View

15.

Wang Z, Zang C, Rosenfeld J, Schones D, Barski A, Cuddapah S . Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008; 40(7):897-903. PMC: 2769248. DOI: 10.1038/ng.154. View

16.

Cohen B, Mitra R, Hughes J, Church G . A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression. Nat Genet. 2000; 26(2):183-6. DOI: 10.1038/79896. View

17.

Kikuta H, LaPlante M, Navratilova P, Komisarczuk A, Engstrom P, Fredman D . Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates. Genome Res. 2007; 17(5):545-55. PMC: 1855176. DOI: 10.1101/gr.6086307. View

18.

Hurst L, Pal C, Lercher M . The evolutionary dynamics of eukaryotic gene order. Nat Rev Genet. 2004; 5(4):299-310. DOI: 10.1038/nrg1319. View

19.

Creyghton M, Cheng A, Welstead G, Kooistra T, Carey B, Steine E . Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A. 2010; 107(50):21931-6. PMC: 3003124. DOI: 10.1073/pnas.1016071107. View

20.

Kim A, Zhao H, Ifrim I, Dean A . Beta-globin intergenic transcription and histone acetylation dependent on an enhancer. Mol Cell Biol. 2007; 27(8):2980-6. PMC: 1899946. DOI: 10.1128/MCB.02337-06. View