Science - USA (2022-02-04)

as also indicated by the profiles along this
flight track (Fig. 4D). Using the GEOS-Chem
model as an intermediary, we find that the
nighttime detection of isoprene by CrIS over
tropical South America is consistent with down-
wind levels of OA observed by aircraft.
Previous studies based on ensemble ana-
lyses of aircraft observations have noted that
chemistry models are missing a substantial
source of free tropospheric OA ( 22 , 23 ). In-
creasing the anthropogenic component of OA
helps to explain the measurement-model gap
near source regions ( 24 ) but fails to reconcile
measurements in the remote atmosphere ( 23 ).
Similarly, improved knowledge of atmospheric
chemistryonlypartlyaddressesthemodelbias
( 25 ). Our analysis suggests that over the tropics
more attention should be given to the mag-
nitude and distribution of isoprene and the
chemical and physical processes that deter-
mine its transport to the free troposphere at
sunset, in addition to studying the atmospheric
fate of isoprene oxidation products. By virtue
of its atmospheric lifetime, IEPOX-SOA can be
transported across the tropical upper tropo-
sphere, where it represents about one-third of
total OA ( 16 ), eventually subsiding to provide a
large seasonal supply of cloud condensation
nuclei in the lower troposphere ( 26 – 29 ).

REFERENCES AND NOTES

1. T. D. Sharkey, A. E. Wiberley, A. R. Donohue,Ann. Bot. 101 ,
   5 – 18 (2008).


2. E. Pegoraro, A. Rey, L. Abrell, J. Van Haren, G. Lin,Glob.
   Change Biol. 12 , 456–469 (2006).


3. A. Guentheret al.,Atmos. Chem. Phys. 6 , 3181–3210 (2006).


4. A. Arnethet al.,Atmos. Chem. Phys. 11 , 8037–8052 (2011).


5. T. Stavrakouet al.,Atmos. Chem. Phys. 14 , 4587–4605 (2014).


6. P. I. Palmeret al.,J. Geophys. Res. 108 , 4180, (2003).


7. P. I. Palmeret al.,J. Geophys. Res. 111 , D12315 (2006).


8. D. B. Milletet al.,J. Geophys. Res. 113 , D02307 (2008).


9. F. Paulotet al.,Science 325 , 730–733 (2009).


10. J. D. Surrattet al.,Proc. Natl. Acad. Sci. U.S.A. 107 ,
    6640 – 6645 (2010).


11. C. J. Gastonet al.,Environ. Sci. Technol. 48 , 11178–11186 (2014).


12. Y. Zhanget al.,Environ. Sci. Technol. Lett. 5 , 167–174 (2018).


13. E. L. D’Ambroet al.,Atmos. Chem. Phys. 19 , 11253– 11265
    (2019).


14. D. Fuet al.,Nat. Commun. 10 , 3811 (2019).


15. K. C. Wellset al.,Nature 585 , 225–233 (2020).


16. See supplementary materials.


17. R. Siddans, L. Ventress, D. Knappett, B. Kerridge, RAL
    extended Infrared Microwave Sounder (IMS) retrievals of
    atmospheric and surface properties: Subset of four selected
    months in 2018 from Suomi-NPP (2021).


18. E. A. Maraiset al.,Atmos. Chem. Phys. 16 , 1603–1618 (2016).


19. S. Wofsyet al., ATom: Merged atmospheric chemistry, trace
    gases, and aerosols (Oak Ridge National Laboratory, 2018).


20. K. H. Bates, D. J. Jacob,Atmos. Chem. Phys. 19 , 9613– 9640
    (2019).


21. M. P. Barkleyet al.,J. Geophys. Res. 113 , D20304 (2008).


22. C. L. Healdet al.,Geophys. Res. Lett. 32 , n/a (2005).


23. C. L. Healdet al.,Atmos. Chem. Phys. 11 , 12673–12696 (2011).


24. V. Spracklenet al.,Atmos. Chem. Phys. 11 , 12109–12136 (2011).


25. S. J. Paiet al.,Atmos. Chem. Phys. 20 , 2637–2665 (2020).


26. M. O. Andreaeet al.,Atmos. Chem. Phys. 18 , 921–961 (2018).


27. C. Schulzet al.,Atmos. Chem. Phys. 18 , 14979–15001 (2018).


28. C. J. Williamsonet al.,Nature 574 , 399–403 (2019).


29. Y. Liuet al.,Sci. Adv. 4 , eaar2547 (2018).

ACKNOWLEDGMENTS
We thank the ATom team for collecting and distributing the data,
particularly P. Campuzano-Jost and J.-L. Jimenez (U. Colorado,

Boulder) for sharing their AMS-60s data; the ACRIDICON-

CHUVA team, including C. Schulz and J. Schneider (MPI, Mainz),

for advice regarding their aerosol measurements; D. Jo

(U. Colorado, Boulder) for useful discussions on modeling

IEPOX-SOA; the GEOS-Chem community, particularly the

team at Harvard who help maintain the GEOS-Chem model;

and the NASA Global Modeling and Assimilation Office (GMAO)

who provide the meteorological reanalysis data products.

Funding:All authors acknowledge support from the UK

National Centre for Earth Observation funded by the National

Environment Research Council (NE/R016518/1 and NE/R000115/

1).Author contributions:P.I.P. and M.R.M. originated the

ideas, with contributions from B.J.K., designed the experiments,

and led the data analysis; M.R.M. led the model calculations;

R.S. and B.J.K. developed the Infrared Microwave Sounder

(IMS) isoprene data product and provided technical information

that supported the data analysis; D.P.M. provided information

about non-isoprene absorbers in the fitting window; P.I.P.

led the writing of the paper, with contributions from coauthors

M.R.M., R.S., B.J.K., and D.P.M.Competing interests:The

authors declare no competing interests.Data and materials

availability:All the data and materials used in this study are

freely available. The IMS isoprene data are available from ( 17 ).

Data from the NASA ATom campaign are available from ( 19 ).

TROPOMI tropospheric NO 2 and HCHO data are freely available

from https://scihub.copernicus.eu/. The GEOS-Chem model

code is available at http://www.geos-chem.org.

SUPPLEMENTARY MATERIALS

science.org/doi/10.1126/science.abg4506

Materials and Methods

Supplementary Text

Figs. S1 to S23

Tables S1 and S2

References ( 30 Ð 76 )

7 January 2021; accepted 28 December 2021

10.1126/science.abg4506

GENE REGULATION

Genome organization controls transcriptional

dynamics during development

Philippe J. Batut*, Xin Yang Bing, Zachary Sisco, João Raimundo, Michal Levo, Michael S. Levine*

Past studies offer contradictory claims for the role of genome organization in the regulation of gene

activity. Here, we show through high-resolution chromosome conformation analysis that theDrosophila

genome is organized by two independent classes of regulatory sequences, tethering elements and

insulators. Quantitative live imaging and targeted genome editing demonstrate that this two-tiered

organization is critical for the precise temporal dynamics of Hox gene transcription during development.

Tethering elements mediate long-range enhancer-promoter interactions and foster fast activation

kinetics. Conversely, the boundaries of topologically associating domains (TADs) prevent spurious

interactions with enhancers and silencers located in neighboring TADs. These two levels of genome

organization operate independently of one another to ensure precision of transcriptional dynamics and

the reliability of complex patterning processes.

G

enome organization is emerging as a

potentially important facet of gene

regulation ( 1 – 5 ). Because transcriptional

enhancers often reside far from their

target promoters, chromatin folding may

guide the timely and specific establishment of

regulatory interactions ( 1 , 3 , 4 , 6 – 10 ). Although

long-range enhancer-promoter contacts are

prevalent, it remains unclear whether they

actually determine transcriptional activity

( 9 , 11 ). Boundary elements partition chromo-

somes into topologically associating domains

(TADs) ( 7 , 12 ), whose importance for gene

regulation remains controversial ( 8 , 13 – 16 ).

There is also an unresolved dichotomy between

elements that promote and prevent enhancer-

promoter interactions, because CTCF binding

sites have been implicated in both ( 7 , 9 , 17 ). We

show here that distinct classes of regulatory

elements mediate these opposing functions

genome-wide: Dedicated tethering elements

foster appropriate enhancer-promoter inter-

actions and are key to fast activation kinetics,

whereas insulators prevent spurious inter-

actions and regulatory interference between

neighboring TADs.

We characterized genome organization at

single-nucleosome resolution in developing

Drosophilaembryos using Micro-C ( 18 ). We

focused on the critical ~60-min period preced-

ing gastrulation, when the fate map of the

embryo is established by localized transcription

of a cascade of patterning genes, culminat-

ing with the Hox genes that specify segment

identity. Analysis of theAntennapediagene

complex (ANT-C), one of two Hox gene clusters

and an archetype of regulatory precision, reveals

an intricate hierarchical organization. Insulators

partition the locus into a series of TADs, whereas

tethering elements mediate specific intra-

TAD focal contacts between promoters ofScr

andAntpand their distal regulatory regions

(Fig. 1A and fig. S1).

The entire genome is similarly organized by

2034 insulators and 620 tethering elements.

Insulators and tethers display notably little

physical overlap (Fig. 1B) and have sharply

contrasting chromatin signatures (Fig. 1C;

566 4 FEBRUARY 2022•VOL 375 ISSUE 6580 science.orgSCIENCE

Lewis-Sigler Institute for Integrative Genomics, Princeton

University, Princeton, NJ, USA.

*Corresponding author. Email: [email protected] (M.S.L.);

[email protected] (P.J.B.)

RESEARCH | REPORTS