Anders Sejr Hansen
@andersshansen.bsky.social
Associate Professor at MIT BE : http://ashansenlab.com
Interested in understanding the relationship between 3D genome structure and function
Interested in understanding the relationship between 3D genome structure and function
Wonderful to see the beautiful preprint from Sabate et al now published - TADs are also dynamic structures in human cells, with remarkably similar parameters between mESCs and HCT116 cells
www.nature.com/articles/s41...
www.nature.com/articles/s41...
November 15, 2025 at 5:24 PM
Wonderful to see the beautiful preprint from Sabate et al now published - TADs are also dynamic structures in human cells, with remarkably similar parameters between mESCs and HCT116 cells
www.nature.com/articles/s41...
www.nature.com/articles/s41...
(4/n) Why are microcompartments stronger in mitosis?
Simulations from @irate-physicist.bsky.social point to compaction.
Mitotic chr 2-3x more compacted --> lower configurational entropy --> lower entropic penalty for forming microcompartments --> microcompartment formation favored in mitosis!
Simulations from @irate-physicist.bsky.social point to compaction.
Mitotic chr 2-3x more compacted --> lower configurational entropy --> lower entropic penalty for forming microcompartments --> microcompartment formation favored in mitosis!
October 20, 2025 at 6:48 PM
(4/n) Why are microcompartments stronger in mitosis?
Simulations from @irate-physicist.bsky.social point to compaction.
Mitotic chr 2-3x more compacted --> lower configurational entropy --> lower entropic penalty for forming microcompartments --> microcompartment formation favored in mitosis!
Simulations from @irate-physicist.bsky.social point to compaction.
Mitotic chr 2-3x more compacted --> lower configurational entropy --> lower entropic penalty for forming microcompartments --> microcompartment formation favored in mitosis!
(3/n) Do mitotic microcompartments have a transcriptional function?
Prior work from @chrishsiung.bsky.social Gerd Blobel discovered 'mitotic transcriptional spiking', where ~half of genes transcriptionally spike in mitosis.
We now show that microcompartment dot number and strength predicts spiking
Prior work from @chrishsiung.bsky.social Gerd Blobel discovered 'mitotic transcriptional spiking', where ~half of genes transcriptionally spike in mitosis.
We now show that microcompartment dot number and strength predicts spiking
October 20, 2025 at 6:45 PM
(3/n) Do mitotic microcompartments have a transcriptional function?
Prior work from @chrishsiung.bsky.social Gerd Blobel discovered 'mitotic transcriptional spiking', where ~half of genes transcriptionally spike in mitosis.
We now show that microcompartment dot number and strength predicts spiking
Prior work from @chrishsiung.bsky.social Gerd Blobel discovered 'mitotic transcriptional spiking', where ~half of genes transcriptionally spike in mitosis.
We now show that microcompartment dot number and strength predicts spiking
(2/n) Previously, it was thought that all 'patterned 3D genome structure' is entirely lost in mitosis. Using High-Res RCMC, we unexpectedly find that not only do microcompartments form during mitosis, they are actually stronger in mitosis than in interphase.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
October 20, 2025 at 6:41 PM
(2/n) Previously, it was thought that all 'patterned 3D genome structure' is entirely lost in mitosis. Using High-Res RCMC, we unexpectedly find that not only do microcompartments form during mitosis, they are actually stronger in mitosis than in interphase.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Check out Shdema's preprint that uses high-res Micro-C to delineate 3D genome structure in three tomato species highlighting both activating and repressive loops and the independence of looping and insulation in tomato:
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
October 17, 2025 at 12:50 AM
Check out Shdema's preprint that uses high-res Micro-C to delineate 3D genome structure in three tomato species highlighting both activating and repressive loops and the independence of looping and insulation in tomato:
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
It's also nice to see a very rigorous and careful approach to analyzing interactions in live-cell imaging data subject to noise. Direct simple thresholding of such data will inevitably give artefactual numbers.
September 24, 2025 at 7:13 PM
It's also nice to see a very rigorous and careful approach to analyzing interactions in live-cell imaging data subject to noise. Direct simple thresholding of such data will inevitably give artefactual numbers.
Really enjoyed reading the new @lucagiorgetti.bsky.social lab preprint that makes the case that not all E-P interactions are created equal - it is the subset of long-lived extrusion-mediated E-P interactions that are most transcriptionally important:
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
September 24, 2025 at 7:08 PM
Really enjoyed reading the new @lucagiorgetti.bsky.social lab preprint that makes the case that not all E-P interactions are created equal - it is the subset of long-lived extrusion-mediated E-P interactions that are most transcriptionally important:
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Asking BlueSky for help: For a review, I am trying to accurately credit the first paper that measured pairwise 3D distances between 2 pieces of DNA on the same chromosome (or cosmid). Is Trask 1989 the first?
I know of earlier single-locus papers (1982).
www.sciencedirect.com/science/arti...
I know of earlier single-locus papers (1982).
www.sciencedirect.com/science/arti...
September 21, 2025 at 6:54 PM
Asking BlueSky for help: For a review, I am trying to accurately credit the first paper that measured pairwise 3D distances between 2 pieces of DNA on the same chromosome (or cosmid). Is Trask 1989 the first?
I know of earlier single-locus papers (1982).
www.sciencedirect.com/science/arti...
I know of earlier single-locus papers (1982).
www.sciencedirect.com/science/arti...
Jamie Drayton and I were fortunate to contribute some RCMC analyses to this beautiful paper from Eder, Moene...van Steensel that systematically maps the relationship between enhancer location and gene expression (and nice to see RCMC predict expression in Fig 2H-I):
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
September 19, 2025 at 7:41 PM
Jamie Drayton and I were fortunate to contribute some RCMC analyses to this beautiful paper from Eder, Moene...van Steensel that systematically maps the relationship between enhancer location and gene expression (and nice to see RCMC predict expression in Fig 2H-I):
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Congratulations to Masahiro Nagano on his new paper on STAG3-cohesin.
STAG3-cohesin has a much shorter residence time which leads to altered 3D genome organization and STAG3-cohesin is important for male germ cell differentiation.
www.nature.com/articles/s41...
STAG3-cohesin has a much shorter residence time which leads to altered 3D genome organization and STAG3-cohesin is important for male germ cell differentiation.
www.nature.com/articles/s41...
August 26, 2025 at 4:18 PM
Congratulations to Masahiro Nagano on his new paper on STAG3-cohesin.
STAG3-cohesin has a much shorter residence time which leads to altered 3D genome organization and STAG3-cohesin is important for male germ cell differentiation.
www.nature.com/articles/s41...
STAG3-cohesin has a much shorter residence time which leads to altered 3D genome organization and STAG3-cohesin is important for male germ cell differentiation.
www.nature.com/articles/s41...
This seems like a really important paper comparing chromosome tracing methods, demonstrating that classical denaturing DNA-FISH and chromosome tracing leads to substantial distortion of 3D genome structure, likely due to the high-temperatures involved (70-90C):
www.nature.com/articles/s41...
www.nature.com/articles/s41...
July 20, 2025 at 7:39 PM
This seems like a really important paper comparing chromosome tracing methods, demonstrating that classical denaturing DNA-FISH and chromosome tracing leads to substantial distortion of 3D genome structure, likely due to the high-temperatures involved (70-90C):
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Congratulations to Dr. Viraat Goel and Dr. Domenic Narducci @domenicnarducci.bsky.social , both new PhDs in Biological Engineering from the lab 🎉
May 28, 2025 at 10:43 PM
Congratulations to Dr. Viraat Goel and Dr. Domenic Narducci @domenicnarducci.bsky.social , both new PhDs in Biological Engineering from the lab 🎉
(13/13) All credit to @matteomazzocca.bsky.social @domenicnarducci.bsky.social Simon Grosse-Holz @jessematthias.bsky.social and to all who helped along the way.
Thanks to Abberior - MINFLUX is awesome!
We would love critical feedback.
Full preprint here www.biorxiv.org/content/10.1...
Thanks to Abberior - MINFLUX is awesome!
We would love critical feedback.
Full preprint here www.biorxiv.org/content/10.1...
May 15, 2025 at 1:44 PM
(13/13) All credit to @matteomazzocca.bsky.social @domenicnarducci.bsky.social Simon Grosse-Holz @jessematthias.bsky.social and to all who helped along the way.
Thanks to Abberior - MINFLUX is awesome!
We would love critical feedback.
Full preprint here www.biorxiv.org/content/10.1...
Thanks to Abberior - MINFLUX is awesome!
We would love critical feedback.
Full preprint here www.biorxiv.org/content/10.1...
(12/n) Strong subdiffusion may also reconcile apparent discrepancy between action-at-a-distance (e.g. condensate, >200 nm) and direct contact E-P models
Strong subdiffusion makes frequent contact inevitable for E-P separations of ~200 nm.
Frequent local CRE contacts also predict microcompartments
Strong subdiffusion makes frequent contact inevitable for E-P separations of ~200 nm.
Frequent local CRE contacts also predict microcompartments
May 15, 2025 at 1:40 PM
(12/n) Strong subdiffusion may also reconcile apparent discrepancy between action-at-a-distance (e.g. condensate, >200 nm) and direct contact E-P models
Strong subdiffusion makes frequent contact inevitable for E-P separations of ~200 nm.
Frequent local CRE contacts also predict microcompartments
Strong subdiffusion makes frequent contact inevitable for E-P separations of ~200 nm.
Frequent local CRE contacts also predict microcompartments
(11/n) Implications for E-P search
- Nucleus is crowded (~400 genes + ~8,000 per um^3)
- Finding nearby (within few hundred kb) enhancers is very efficient
- Very distal and generally non-cognate enhancers (>Mb) are avoided unless facilitated by other mechanisms (e.g. loop extrusion)
- Nucleus is crowded (~400 genes + ~8,000 per um^3)
- Finding nearby (within few hundred kb) enhancers is very efficient
- Very distal and generally non-cognate enhancers (>Mb) are avoided unless facilitated by other mechanisms (e.g. loop extrusion)
May 15, 2025 at 1:36 PM
(11/n) Implications for E-P search
- Nucleus is crowded (~400 genes + ~8,000 per um^3)
- Finding nearby (within few hundred kb) enhancers is very efficient
- Very distal and generally non-cognate enhancers (>Mb) are avoided unless facilitated by other mechanisms (e.g. loop extrusion)
- Nucleus is crowded (~400 genes + ~8,000 per um^3)
- Finding nearby (within few hundred kb) enhancers is very efficient
- Very distal and generally non-cognate enhancers (>Mb) are avoided unless facilitated by other mechanisms (e.g. loop extrusion)
(10/n) Strong subdiffusion (a~0.3) is not fast or slow per se.
Rather, it makes finding nearby things extremely efficient and finding very distal things nearly impossible.
median first passage time estimates:
~4 ms to find 100 nm distal target
>25 hours to find 1300 nm distal target
Rather, it makes finding nearby things extremely efficient and finding very distal things nearly impossible.
median first passage time estimates:
~4 ms to find 100 nm distal target
>25 hours to find 1300 nm distal target
May 15, 2025 at 1:32 PM
(10/n) Strong subdiffusion (a~0.3) is not fast or slow per se.
Rather, it makes finding nearby things extremely efficient and finding very distal things nearly impossible.
median first passage time estimates:
~4 ms to find 100 nm distal target
>25 hours to find 1300 nm distal target
Rather, it makes finding nearby things extremely efficient and finding very distal things nearly impossible.
median first passage time estimates:
~4 ms to find 100 nm distal target
>25 hours to find 1300 nm distal target
(9/n) Perturbations affect chromatin dynamics (consistent with prior work from @kazu-maeshima.bsky.social @lucagiorgetti.bsky.social @ellenberglab.bsky.social and many others) but effects are generally modest without affecting exponent.
Only loop extrusion affects exponent.
Only loop extrusion affects exponent.
May 15, 2025 at 1:25 PM
(9/n) Perturbations affect chromatin dynamics (consistent with prior work from @kazu-maeshima.bsky.social @lucagiorgetti.bsky.social @ellenberglab.bsky.social and many others) but effects are generally modest without affecting exponent.
Only loop extrusion affects exponent.
Only loop extrusion affects exponent.
(8/n) Integrating MINFLUX+SPT+SRLCI and jointly fitting them using a Bayesian method, we can reach 6-7 OOM:
alpha~0.3 in U2OS cells across full 6+ OOM
mESC chromatin dynamics does not follow power law, invalidating mESC descriptions using single exponent 🤔
Both mESC+U2OS show strong subdiffusion
alpha~0.3 in U2OS cells across full 6+ OOM
mESC chromatin dynamics does not follow power law, invalidating mESC descriptions using single exponent 🤔
Both mESC+U2OS show strong subdiffusion
May 15, 2025 at 1:22 PM
(8/n) Integrating MINFLUX+SPT+SRLCI and jointly fitting them using a Bayesian method, we can reach 6-7 OOM:
alpha~0.3 in U2OS cells across full 6+ OOM
mESC chromatin dynamics does not follow power law, invalidating mESC descriptions using single exponent 🤔
Both mESC+U2OS show strong subdiffusion
alpha~0.3 in U2OS cells across full 6+ OOM
mESC chromatin dynamics does not follow power law, invalidating mESC descriptions using single exponent 🤔
Both mESC+U2OS show strong subdiffusion
(7/n) MINFLUX had not previously been used for chromatin dynamics.
MINFLUX @stefanhelllabs.bsky.social is transformative and allows tracking at microsecond timescale, but procedure introduces bias for recurrent motion --> by carefully simulating MINFLUX to optimize L we can avoid this bias.
MINFLUX @stefanhelllabs.bsky.social is transformative and allows tracking at microsecond timescale, but procedure introduces bias for recurrent motion --> by carefully simulating MINFLUX to optimize L we can avoid this bias.
May 15, 2025 at 1:14 PM
(7/n) MINFLUX had not previously been used for chromatin dynamics.
MINFLUX @stefanhelllabs.bsky.social is transformative and allows tracking at microsecond timescale, but procedure introduces bias for recurrent motion --> by carefully simulating MINFLUX to optimize L we can avoid this bias.
MINFLUX @stefanhelllabs.bsky.social is transformative and allows tracking at microsecond timescale, but procedure introduces bias for recurrent motion --> by carefully simulating MINFLUX to optimize L we can avoid this bias.
(6/n) We used
- 3 techniques: MINFLUX, SPT, SRLCI
- 2 labels: Histone H2B (global, pioneered by @kazu-maeshima.bsky.social ) and Fbn2 locus (local, www.science.org/doi/full/10.... )
- 2 cell lines: human U2OS, mESCs
- 4 perturbations: Loop extrusion, Transcription, Histone Acetylation, Supercoiling
- 3 techniques: MINFLUX, SPT, SRLCI
- 2 labels: Histone H2B (global, pioneered by @kazu-maeshima.bsky.social ) and Fbn2 locus (local, www.science.org/doi/full/10.... )
- 2 cell lines: human U2OS, mESCs
- 4 perturbations: Loop extrusion, Transcription, Histone Acetylation, Supercoiling
May 15, 2025 at 1:10 PM
(6/n) We used
- 3 techniques: MINFLUX, SPT, SRLCI
- 2 labels: Histone H2B (global, pioneered by @kazu-maeshima.bsky.social ) and Fbn2 locus (local, www.science.org/doi/full/10.... )
- 2 cell lines: human U2OS, mESCs
- 4 perturbations: Loop extrusion, Transcription, Histone Acetylation, Supercoiling
- 3 techniques: MINFLUX, SPT, SRLCI
- 2 labels: Histone H2B (global, pioneered by @kazu-maeshima.bsky.social ) and Fbn2 locus (local, www.science.org/doi/full/10.... )
- 2 cell lines: human U2OS, mESCs
- 4 perturbations: Loop extrusion, Transcription, Histone Acetylation, Supercoiling
(5/n) To give a sense of difficulty, recent preprint (Lee-2025) optimized locus tracking to reach ultra-resolution got 3 OOM (0.5-1800 sec, range of 3,600)
By integrating MINFLUX, we span 0.0002 to 7200 sec reaching range of 36,000,000 to span 7 OOM in time to map chromatin dynamics in live cells
By integrating MINFLUX, we span 0.0002 to 7200 sec reaching range of 36,000,000 to span 7 OOM in time to map chromatin dynamics in live cells
May 15, 2025 at 1:02 PM
(5/n) To give a sense of difficulty, recent preprint (Lee-2025) optimized locus tracking to reach ultra-resolution got 3 OOM (0.5-1800 sec, range of 3,600)
By integrating MINFLUX, we span 0.0002 to 7200 sec reaching range of 36,000,000 to span 7 OOM in time to map chromatin dynamics in live cells
By integrating MINFLUX, we span 0.0002 to 7200 sec reaching range of 36,000,000 to span 7 OOM in time to map chromatin dynamics in live cells
(4/n) However, statistically rigorous power law fitting requires 2 Orders Of Magnitude (OOM) in both x (time) and y (MSD) @theosysbio.bsky.social
MSD~time^alpha:
If a~0.4 (fractal globule), need 5 OOM in time
If a~0.3, need 7 OOM in time
7 OOM in time means a movie with >10,000,000 frames 😱
MSD~time^alpha:
If a~0.4 (fractal globule), need 5 OOM in time
If a~0.3, need 7 OOM in time
7 OOM in time means a movie with >10,000,000 frames 😱
May 15, 2025 at 12:57 PM
(4/n) However, statistically rigorous power law fitting requires 2 Orders Of Magnitude (OOM) in both x (time) and y (MSD) @theosysbio.bsky.social
MSD~time^alpha:
If a~0.4 (fractal globule), need 5 OOM in time
If a~0.3, need 7 OOM in time
7 OOM in time means a movie with >10,000,000 frames 😱
MSD~time^alpha:
If a~0.4 (fractal globule), need 5 OOM in time
If a~0.3, need 7 OOM in time
7 OOM in time means a movie with >10,000,000 frames 😱
(3/n) Precisely determining alpha is extremely important because tiny alpha changes massively affect search times.
Increase E-P separation from 10 to 500 kb:
if a~0.8, search time increases 300-fold
if a~0.2, search time increases 10-billion fold
Cannot understand E-P dynamics without alpha
Increase E-P separation from 10 to 500 kb:
if a~0.8, search time increases 300-fold
if a~0.2, search time increases 10-billion fold
Cannot understand E-P dynamics without alpha
May 15, 2025 at 12:50 PM
(3/n) Precisely determining alpha is extremely important because tiny alpha changes massively affect search times.
Increase E-P separation from 10 to 500 kb:
if a~0.8, search time increases 300-fold
if a~0.2, search time increases 10-billion fold
Cannot understand E-P dynamics without alpha
Increase E-P separation from 10 to 500 kb:
if a~0.8, search time increases 300-fold
if a~0.2, search time increases 10-billion fold
Cannot understand E-P dynamics without alpha
(2/n) Chromatin dynamics govern all nuclear processes w, DNA movement (e.g. E-P search, DNA repair).
Mean Squared Displacement (MSD) should follow power law: MSD ~ time^alpha
fBm simulation shows this: a~0.25 oversamples local environment, whereas Brownian motion a=1 explores more globally.
Mean Squared Displacement (MSD) should follow power law: MSD ~ time^alpha
fBm simulation shows this: a~0.25 oversamples local environment, whereas Brownian motion a=1 explores more globally.
May 15, 2025 at 12:46 PM
(2/n) Chromatin dynamics govern all nuclear processes w, DNA movement (e.g. E-P search, DNA repair).
Mean Squared Displacement (MSD) should follow power law: MSD ~ time^alpha
fBm simulation shows this: a~0.25 oversamples local environment, whereas Brownian motion a=1 explores more globally.
Mean Squared Displacement (MSD) should follow power law: MSD ~ time^alpha
fBm simulation shows this: a~0.25 oversamples local environment, whereas Brownian motion a=1 explores more globally.
(1/n) Thread @matteomazzocca.bsky.social @domenicnarducci.bsky.social Simon Grosse-Holz @jessematthias.bsky.social preprint
Q: how does chromatin move?
Using MINFLUX, SPT & SRLCI, we track chromatin dynamics across 7 orders of magnitude in time to provide answers www.biorxiv.org/content/10.1...
Q: how does chromatin move?
Using MINFLUX, SPT & SRLCI, we track chromatin dynamics across 7 orders of magnitude in time to provide answers www.biorxiv.org/content/10.1...
May 15, 2025 at 12:37 PM
(1/n) Thread @matteomazzocca.bsky.social @domenicnarducci.bsky.social Simon Grosse-Holz @jessematthias.bsky.social preprint
Q: how does chromatin move?
Using MINFLUX, SPT & SRLCI, we track chromatin dynamics across 7 orders of magnitude in time to provide answers www.biorxiv.org/content/10.1...
Q: how does chromatin move?
Using MINFLUX, SPT & SRLCI, we track chromatin dynamics across 7 orders of magnitude in time to provide answers www.biorxiv.org/content/10.1...