[en] The cohesin complex is central to chromatin looping, but mechanisms by which these long-range chromatin interactions are formed and persist remain unclear. We demonstrate that interactions between a transcription factor (TF) and the cohesin loader NIPBL regulate enhancer-dependent gene activity. Using mass spectrometry, genome mapping, and single-molecule tracking methods, we demonstrate that the glucocorticoid (GC) receptor (GR) interacts with NIPBL and the cohesin complex at the chromatin level, promoting loop extrusion and long-range gene regulation. Real-time single-molecule experiments show that loss of cohesin markedly diminishes the concentration of TF molecules at specific nuclear confinement sites, increasing TF local concentration and promoting gene regulation. Last, patient-derived acute myeloid leukemia cells harboring cohesin mutations exhibit a reduced response to GCs, suggesting that the GR-NIPBL-cohesin interaction is defective in these patients, resulting in poor response to GC treatment.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Rinaldi, Lorenzo ✱; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Fettweis, Grégory ✱; Université de Liège - ULiège > Département des sciences de la vie > Génétique et biologie moléculaires animales ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Kim, Sohyoung ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Garcia, David A; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA ; Department of Physics, University of Maryland, College Park, MD 20742, USA
Fujiwara, Saori ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Johnson, Thomas A ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Tettey, Theophilus T ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Ozbun, Laurent ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA ; High-Throughput Imaging Facility (HiTIF), Center for Cancer Research (CCR), NCI/NIH, Bethesda, MD 20892, USA
Pegoraro, Gianluca ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA ; High-Throughput Imaging Facility (HiTIF), Center for Cancer Research (CCR), NCI/NIH, Bethesda, MD 20892, USA
Puglia, Michele; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
Blagoev, Blagoy ; Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
Upadhyaya, Arpita; Department of Physics, University of Maryland, College Park, MD 20742, USA ; Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA
Stavreva, Diana A ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Hager, Gordon L ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
✱ These authors have contributed equally to this work.
Language :
English
Title :
The glucocorticoid receptor associates with the cohesin loader NIPBL to promote long-range gene regulation.
Publication date :
April 2022
Journal title :
Science Advances
eISSN :
2375-2548
Publisher :
American Association for the Advancement of Science, United States
Volume :
8
Issue :
13
Pages :
eabj8360
Peer reviewed :
Peer Reviewed verified by ORBi
Funding text :
We thank M. Kanemaki for providing the HCT116 RAD21mAID cells. We thank J. Taub for providing the DS-AMKL cells. We thank the Center for Cancer Research (CCR) Genomics Core, CCR Sequencing Facility, Flow Cytometry, and High-Throughput Facility at NCI. We would like to thank T. Karpova and D. Ball at the Optical Microscopy Core at NIH. We thank P. Rocha, E. Arda, and L. Wang for technical support to perform Micro-C and HiChIP experiments. This work used the computational resources of the NIH HPC Biowulf cluster. We thank G. Vahedi and S. Yoon from Penn University of Medicine for technical support to run the Stripenn algorithm. We would like to thank the Danish National Research Foundation (DNRF grant no. 141 to ATLAS) and Novo Nordisk Foundation (NNF18OC0052768). We thank A. Lillich, NIH Library Editing Service, for manuscript editing assistance. The current affiliation of S.F. is the Kanagawa Cancer Center of Yokohama, Japan, while G.F. is at the University of Liège, Belgium. D.A.G. is currently employed at the Boston Consulting Group, Chicago, IL. Funding: S.F. was supported by the JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH. A.U. acknowledges support from NSF PHY 1806903 and NSF PHY 1915534. L.R. was supported by the EMBO long-term postdoctoral fellowship. This work was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Author contributions: L.R., G.F., and G.L.H. conceived the study and wrote the manuscript with input of all the other coauthors. L.R. performed and analyzed genomic experiments such as ChIP-seq and HiChIP. L.R. and T.A.J. performed the Micro-C experiments, analyzed by L.R. and S.K. G.F. performed ChIP-SICAP, HCR, IP, PLA, and IF, helped by D.A.S. G.F., M.P., and B.B. analyzed ChIP-SICAP data, while HCR was analyzed by G.F. and G.P. L.R. and G.F. performed SMT, analyzed by D.A.G. and G.F. with valuable advice provided by A.U. S.F. performed ATAC-seq, analyzed by L.R. and S.K. T.T.T. performed TNF-RNA-seq experiments, analyzed by L.R. and S.K. G.L.H. supervised the research. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. The GEO accession number for the genomic data is GSE162617.
E. H. Finn, T. Misteli, Molecular basis and biological function of variability in spatial genome organization. Science 365, eaaw9498 (2019).
S. Kim, J. Shendure, Mechanisms of Interplay between transcription factors and the 3D genome. Mol. Cell 76, 306–319 (2019).
Q. Szabo, A. Donjon, I. Jerković, G. L. Papadopoulos, T. Cheutin, B. Bonev, E. P. Nora, B. G. Bruneau, F. Bantignies, G. Cavalli, Regulation of single-cell genome organization into TADs and chromatin nanodomains. Nat. Genet. 52, 1151–1157 (2020).
Y. Kim, Z. Shi, H. Zhang, I. J. Finkelstein, H. Yu, Human cohesin compacts DNA by loop extrusion. Science 366, 1345–1349 (2019).
Y. Murayama, C. P. Samora, Y. Kurokawa, H. Iwasaki, F. Uhlmann, Establishment of DNA-DNA interactions by the cohesin ring. Cell 172, 465–477.e15 (2018).
S. S. P. Rao, S.-C. Huang, B. G. St. Hilaire, J. M. Engreitz, E. M. Perez, K.-R. Kieffer-Kwon, A. L. Sanborn, S. E. Johnstone, G. D. Bascom, I. D. Bochkov, X. Huang, M. S. Shamim, J. Shin, D. Turner, Z. Ye, A. D. Omer, J. T. Robinson, T. Schlick, B. E. Bernstein, R. Casellas, E. S. Lander, E. L. Aiden, Cohesin loss eliminates all loop domains. Cell 171, 305–320.e24 (2017).
W. Schwarzer, N. Abdennur, A. Goloborodko, A. Pekowska, G. Fudenberg, Y. Loe-Mie, N. A. Fonseca, W. Huber, C. H. Haering, L. Mirny, F. Spitz, Two independent modes of chromatin organization revealed by cohesin removal. Nature 551, 51–56 (2017).
D. Schmidt, P. C. Schwalie, C. S. Ross-Innes, A. Hurtado, G. D. Brown, J. S. Carroll, P. Flicek, D. T. Odom, A CTCF-independent role for cohesin in tissue-specific transcription. Genome Res. 20, 578–588 (2010).
S. S. P. Rao, M. H. Huntley, N. C. Durand, E. K. Stamenova, I. D. Bochkov, J. T. Robinson, A. L. Sanborn, I. Machol, A. D. Omer, E. S. Lander, E. L. Aiden, A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665–1680 (2014).
J. Holzmann, A. Z. Politi, K. Nagasaka, M. Hantsche-Grininger, N. Walther, B. Koch, J. Fuchs, G. Dürnberger, W. Tang, R. Ladurner, R. R. Stocsits, G. A. Busslinger, B. Novák, K. Mechtler, I. F. Davidson, J. Ellenberg, J. M. Peters, Absolute quantification of cohesin, CTCF and their regulators in human cells. eLife 8, e46269 (2019).
N. J. Petela, T. G. Gligoris, J. Metson, B.-G. Lee, M. Voulgaris, B. Hu, S. Kikuchi, C. Chapard, W. Chen, E. Rajendra, M. Srinivisan, H. Yu, J. Löwe, K. A. Nasmyth, Scc2 is a potent activator of cohesin's ATPase that promotes loading by binding Scc1 without Pds5. Mol. Cell 70, 1134–1148.e7 (2018).
A. S. Hansen, I. Pustova, C. Cattoglio, R. Tjian, X. Darzacq, CTCF and cohesin regulate chromatin loop stability with distinct dynamics. eLife 6, e25776 (2017).
L. Vian, A. Pękowska, S. S. P. Rao, K. R. Kieffer-Kwon, S. Jung, L. Baranello, S. C. Huang, L. el Khattabi, M. Dose, N. Pruett, A. L. Sanborn, A. Canela, Y. Maman, A. Oksanen, W. Resch, X. Li, B. Lee, A. L. Kovalchuk, Z. Tang, S. Nelson, M. di Pierro, R. R. Cheng, I. Machol, B. G. St Hilaire, N. C. Durand, M. S. Shamim, E. K. Stamenova, J. N. Onuchic, Y. Ruan, A. Nussenzweig, D. Levens, E. L. Aiden, R. Casellas, The energetics and physiological impact of cohesin extrusion. Cell 175, 292–294 (2018).
J. Rhodes, D. Mazza, K. Nasmyth, S. Uphoff, Scc2/Nipbl hops between chromosomal cohesin rings after loading. eLife 6, e30000 (2017).
I. F. Davidson, B. Bauer, D. Goetz, W. Tang, G. Wutz, J. M. Peters, DNA loop extrusion by human cohesin. Science 366, 1338–1345 (2019).
M. H. Kagey, J. J. Newman, S. Bilodeau, Y. Zhan, D. A. Orlando, N. L. van Berkum, C. C. Ebmeier, J. Goossens, P. B. Rahl, S. S. Levine, D. J. Taatjes, J. Dekker, R. A. Young, Mediator and cohesin connect gene expression and chromatin architecture. Nature 467, 430–435 (2010).
Y. Zhu, M. Denholtz, H. Lu, C. Murre, Calcium signaling instructs NIPBL recruitment at active enhancers and promoters via distinct mechanisms to reconstruct genome compartmentalization. Genes Dev. 35, 65–81 (2021).
H. Yan, I. Surovtsev, J. F. Williams, M. L. P. Bailey, M. C. King, S. G. J. Mochrie, Extrusion of chromatin loops by a composite loop extrusion factor. Phys. Rev. E 104, 024414 (2021).
H. B. Brandão, P. Paul, A. A. van den Berg, D. Z. Rudner, X. Wang, L. A. Mirny, RNA polymerases as moving barriers to condensin loop extrusion. Proc. Natl. Acad. Sci. U.S.A. 116, 20489–20499 (2019).
E. P. Nora, A. Goloborodko, A.-L. Valton, J. H. Gibcus, A. Uebersohn, N. Abdennur, J. Dekker, L. A. Mirny, B. G. Bruneau, Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization. Cell 169, 930–944.e22 (2017).
F. L. Dily, E. Vidal, Y. Cuartero, J. Quilez, A. S. Nacht, G. P. Vicent, J. Carbonell-Caballero, P. Sharma, J. L. Villanueva-Cañas, R. Ferrari, L. I. De Llober, G. Verde, R. H. G. Wright, M. Beato, Hormone-control regions mediate steroid receptor-dependent genome organization. Genome Res. 29, 29–39 (2019).
A. M. D’Ippolito, I. C. M. Dowell, A. Barrera, L. K. Hong, S. M. Leichter, L. C. Bartelt, C. M. Vockley, W. H. Majoros, A. Safi, L. Song, C. A. Gersbach, G. E. Crawford, T. E. Reddy, Pre-established chromatin interactions mediate the genomic response to glucocorticoids. Cell Syst 7, 146–160.e7 (2018).
S. Cuartero, F. D. Weiss, G. Dharmalingam, Y. Guo, E. Ing-Simmons, S. Masella, I. Robles-Rebollo, X. Xiao, Y. F. Wang, I. Barozzi, D. Djeghloul, M. T. Amano, H. Niskanen, E. Petretto, R. D. Dowell, K. Tachibana, M. U. Kaikkonen, K. A. Nasmyth, B. Lenhard, G. Natoli, A. G. Fisher, M. Merkenschlager, Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation. Nat. Immunol. 19, 932–941 (2018).
D. A. Stavreva, A. Coulon, S. Baek, M. H. Sung, S. John, L. Stixova, M. Tesikova, O. Hakim, T. Miranda, M. Hawkins, J. A. Stamatoyannopoulos, C. C. Chow, G. L. Hager, Dynamics of chromatin accessibility and long-range interactions in response to glucocorticoid pulsing. Genome Res. 25, 845–857 (2015).
M. R. Rafiee, C. Girardot, G. Sigismondo, J. Krijgsveld, Expanding the circuitry of pluripotency by selective isolation of chromatin-associated proteins. Mol. Cell 64, 624–635 (2016).
T. Prenzel, F. Kramer, U. Bedi, S. Nagarajan, T. Beissbarth, S. A. Johnsen, Cohesin is required for expression of the estrogen receptor-alpha (ESR1) gene. Epigenetics Chromatin 5, 13 (2012).
M. Oti, J. Falck, M. A. Huynen, H. Zhou, CTCF-mediated chromatin loops enclose inducible gene regulatory domains. BMC Genomics 17, 252 (2016).
M. R. Mumbach, A. J. Rubin, R. A. Flynn, C. Dai, P. A. Khavari, W. J. Greenleaf, H. Y. Chang, HiChIP: Efficient and sensitive analysis of protein-directed genome architecture. Nat. Methods 13, 919–922 (2016).
S. Bhattacharyya, V. Chandra, P. Vijayanand, F. Ay, Identification of significant chromatin contacts from HiChIP data by FitHiChIP. Nat. Commun. 10, 4221 (2019).
N. Krietenstein, S. Abraham, S. V. Venev, N. Abdennur, J. Gibcus, T.-H. S. Hsieh, K. M. Parsi, L. Yang, R. Maehr, L. A. Mirny, J. Dekker, O. J. Rando, Ultrastructural details of mammalian chromosome architecture. Mol. Cell 78, 554–565.e7 (2020).
T.-H. S. Hsieh, C. Cattoglio, E. Slobodyanyuk, A. S. Hansen, O. J. Rando, R. Tjian, X. Darzacq, Resolving the 3D landscape of transcription-linked mammalian chromatin folding. Mol. Cell 78, 539–553.e8 (2020).
S. Yoon, G. Vahedi, Stripenn detects architectural stripes from chromatin conformation data using computer vision. bioRxiv, 2021.2004.2016.440239 (2021). https://doi.org/10.1101/2021.04.16.440239.
T. Natsume, T. Kiyomitsu, Y. Saga, M. T. Kanemaki, Rapid protein depletion in human cells by auxin-inducible degron tagging with short homology donors. Cell Rep. 15, 210–218 (2016).
J. D. Buenrostro, P. G. Giresi, L. C. Zaba, H. Y. Chang, W. J. Greenleaf, Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213–1218 (2013).
G. Stik, E. Vidal, M. Barrero, S. Cuartero, M. Vila-Casadesús, J. Mendieta-Esteban, T. V. Tian, J. Choi, C. Berenguer, A. Abad, B. Borsari, F. le Dily, P. Cramer, M. A. Marti-Renom, R. Stadhouders, T. Graf, CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response. Nat. Genet. 52, 655–661 (2020).
D. A. Garcia, T. A. Johnson, D. M. Presman, G. Fettweis, K. Wagh, L. Rinaldi, D. A. Stavreva, V. Paakinaho, R. A. M. Jensen, S. Mandrup, A. Upadhyaya, G. L. Hager, An intrinsically disordered region-mediated confinement state contributes to the dynamics and function of transcription factors. Mol. Cell 81, 1484–1498.e6 (2021).
D. M. Presman, D. A. Ball, V. Paakinaho, J. B. Grimm, L. D. Lavis, T. S. Karpova, G. L. Hager, Quantifying transcription factor binding dynamics at the single-molecule level in live cells. Methods 123, 76–88 (2017).
P. K. Koo, M. Weitzman, C. R. Sabanaygam, K. L. van Golen, S. G. Mochrie, Extracting diffusive states of rho GTPase in live cells: Towards in vivo biochemistry. PLoS Comput. Biol. 11, e1004297 (2015).
D. Emerson, P. A. Zhao, K. Klein, C. Ge, L. Zhou, T. Sasaki, L. Yang, S. V. Venvev, J. H. Gibcus, J. Dekker, D. M. Gilbert, E. Phillips-Cremins, Cohesin-mediated loop anchors confine the location of human replication origins. bioRxiv, 2021.2001.2005.425437 (2021). https://doi.org/10.1101/2021.01.05.425437.
S. Cuartero, A. J. Innes, M. Merkenschlager, Towards a better understanding of cohesin mutations in AML. Front. Oncol. 9, 867 (2019).
A. Kon, L. Y. Shih, M. Minamino, M. Sanada, Y. Shiraishi, Y. Nagata, K. Yoshida, Y. Okuno, M. Bando, R. Nakato, S. Ishikawa, A. Sato-Otsubo, G. Nagae, A. Nishimoto, C. Haferlach, D. Nowak, Y. Sato, T. Alpermann, M. Nagasaki, T. Shimamura, H. Tanaka, K. Chiba, R. Yamamoto, T. Yamaguchi, M. Otsu, N. Obara, M. Sakata-Yanagimoto, T. Nakamaki, K. Ishiyama, F. Nolte, W. K. Hofmann, S. Miyawaki, S. Chiba, H. Mori, H. Nakauchi, H. P. Koeffler, H. Aburatani, T. Haferlach, K. Shirahige, S. Miyano, S. Ogawa, Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. Nat. Genet. 45, 1232–1237 (2013).
M. T. Gebru, J. M. Atkinson, M. M. Young, L. Zhang, Z. Tang, Z. Liu, P. Lu, C. M. Dower, L. Chen, C. Annageldiyev, A. Sharma, Y. Imamura Kawasawa, Z. Zhao, B. A. Miller, D. F. Claxton, H. G. Wang, Glucocorticoids enhance the antileukemic activity of FLT3 inhibitors in FLT3-mutant acute myeloid leukemia. Blood 136, 1067–1079 (2020).
D. Malani, A. Murumägi, B. Yadav, M. Kontro, S. Eldfors, A. Kumar, R. Karjalainen, M. M. Majumder, P. Ojamies, T. Pemovska, K. Wennerberg, C. Heckman, K. Porkka, M. Wolf, T. Aittokallio, O. Kallioniemi, Enhanced sensitivity to glucocorticoids in cytarabine-resistant AML. Leukemia 31, 1187–1195 (2017).
S. J. Nair, L. Yang, D. Meluzzi, S. Oh, F. Yang, M. J. Friedman, S. Wang, T. Suter, I. Alshareedah, A. Gamliel, Q. Ma, J. Zhang, Y. Hu, Y. Tan, K. A. Ohgi, R. S. Jayani, P. R. Banerjee, A. K. Aggarwal, M. G. Rosenfeld, Phase separation of ligand-activated enhancers licenses cooperative chromosomal enhancer assembly. Nat. Struct. Mol. Biol. 26, 193–203 (2019).
W. K. Cho, J. H. Spille, M. Hecht, C. Lee, C. Li, V. Grube, I. I. Cisse, Mediator and RNA polymerase II clusters associate in transcription-dependent condensates. Science 361, 412–415 (2018).
E. H. Finn, G. Pegoraro, H. B. Brandão, A.-L. Valton, M. E. Oomen, J. Dekker, L. Mirny, T. Misteli, Extensive heterogeneity and intrinsic variation in spatial genome organization. Cell 176, 1502–1515.e10 (2019).
J. Rodriguez, G. Ren, C. R. Day, K. Zhao, C. C. Chow, D. R. Larson, Intrinsic dynamics of a human gene reveal the basis of expression heterogeneity. Cell 176, 213, 226.e8 (2019).
J. Antony, T. Dasgupta, J. M. Rhodes, M. V. McEwan, C. G. Print, J. M. O’Sullivan, J. A. Horsfield, Cohesin modulates transcription of estrogen-responsive genes. Biochim. Biophys. Acta 1849, 257–269 (2015).
V. Paakinaho, E. E. Swinstead, D. M. Presman, L. Grontved, G. L. Hager, Meta-analysis of chromatin programming by steroid receptors. Cell Rep. 28, 3523, 3534.e22 (2019).
O. Hakim, M. H. Sung, T. C. Voss, E. Splinter, S. John, P. J. Sabo, R. E. Thurman, J. A. Stamatoyannopoulos, W. de Laat, G. L. Hager, Diverse gene reprogramming events occur in the same spatial clusters of distal regulatory elements. Genome Res. 21, 697–706 (2011).
J. M. Alexander, J. Guan, B. Li, L. Maliskova, M. Song, Y. Shen, B. Huang, S. Lomvardas, O. D. Weiner, Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity. eLife 8, e41769 (2019).
N. S. Benabdallah, I. Williamson, R. S. Illingworth, L. Kane, S. Boyle, D. Sengupta, G. R. Grimes, P. Therizols, W. A. Bickmore, Decreased enhancer-promoter proximity accompanying enhancer activation. Mol. Cell 76, 473–484.e7 (2019).
J. Zuin, V. Franke, W. F. J. van IJcken, A. van der Sloot, I. D. Krantz, M. I. J. A. van der Reijden, R. Nakato, B. Lenhard, K. S. Wendt, A cohesin-independent role for NIPBL at promoters provides insights in CdLS. PLOS Genet. 10, e1004153 (2014).
S. Remeseiro, A. Cuadrado, S. Kawauchi, A. L. Calof, A. D. Lander, A. Losada, Reduction of Nipbl impairs cohesin loading locally and affects transcription but not cohesion-dependent functions in a mouse model of Cornelia de Lange syndrome. Biochim. Biophys. Acta 1832, 2097–2102 (2013).
V. Akimov, I. Barrio-Hernandez, S. V. F. Hansen, P. Hallenborg, A. K. Pedersen, D. B. Bekker-Jensen, M. Puglia, S. D. K. Christensen, J. T. Vanselow, M. M. Nielsen, I. Kratchmarova, C. D. Kelstrup, J. V. Olsen, B. Blagoev, UbiSite approach for comprehensive mapping of lysine and N-terminal ubiquitination sites. Nat. Struct. Mol. Biol. 25, 631–640 (2018).
H. M. T. Choi, M. Schwarzkopf, M. E. Fornace, A. Acharya, G. Artavanis, J. Stegmaier, A. Cunha, N. A. Pierce, Third-generation in situ hybridization chain reaction: Multiplexed, quantitative, sensitive, versatile, robust. Development 145, dev165753 (2018).
I. Parenti, F. Diab, S. R. Gil, E. Mulugeta, V. Casa, R. Berutti, R. W. W. Brouwer, V. Dupé, J. Eckhold, E. Graf, B. Puisac, F. Ramos, T. Schwarzmayr, M. M. Gines, T. van Staveren, W. F. J. van IJcken, T. M. Strom, J. Pié, E. Watrin, F. J. Kaiser, K. S. Wendt, MAU2 and nipbl variants impair the heterodimerization of the cohesin loader subunits and cause cornelia de lange syndrome. Cell Rep. 31, 107647 (2020).
A. Dobin, T. R. Gingeras, Mapping RNA-seq reads with STAR. Curr. Protoc. Bioinformatics 51, 11.14.11–11.14.19 (2015).
S. Heinz, C. Benner, N. Spann, E. Bertolino, Y. C. Lin, P. Laslo, J. X. Cheng, C. Murre, H. Singh, C. K. Glass, Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol.Cell 38, 576–589 (2010).
A. Roayaei Ardakany, H. T. Gezer, S. Lonardi, F. Ay, Mustache: Multi-scale detection of chromatin loops from Hi-C and Micro-C maps using scale-space representation. Genome Biol. 21, 256 (2020).
N. C. Durand, J. T. Robinson, M. S. Shamim, I. Machol, J. P. Mesirov, E. S. Lander, E. L. Aiden, Juicebox provides a visualization system for hi-c contact maps with unlimited zoom. Cell Syst 3, 99–101 (2016).
N. Servant, N. Varoquaux, B. R. Lajoie, E. Viara, C. J. Chen, J. P. Vert, E. Heard, J. Dekker, E. Barillot, HiC-Pro: An optimized and flexible pipeline for Hi-C data processing. Genome Biol. 16, 259 (2015).
D. A. Stavreva, D. A. Garcia, G. Fettweis, P. R. Gudla, G. F. Zaki, V. Soni, A. McGowan, G. Williams, A. Huynh, M. Palangat, R. L. Schiltz, T. A. Johnson, D. M. Presman, M. L. Ferguson, G. Pegoraro, A. Upadhyaya, G. L. Hager, Transcriptional bursting and co-bursting regulation by steroid hormone release pattern and transcription factor mobility. Mol. Cell 75, 1161–1177.e11 (2019).
D. A. Garcia, G. Fettweis, D. M. Presman, V. Paakinaho, C. Jarzynski, A. Upadhyaya, G. L. Hager, Power-law behavior of transcription factor dynamics at the single-molecule level implies a continuum affinity model. Nucleic Acids Res. 49, 6605–6620 (2021).
M. I. Love, W. Huber, S. Anders, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
