DNA methylation networks underlying mammalian traits

Amin Haghani; Caesar Z. Li; Todd R. Robeck; Joshua Zhang; Ake T. Lu; Julia Ablaeva; Victoria A. Acosta-Rodríguez; Danielle M. Adams; Abdulaziz N. Alagaili; Javier Almunia; Ajoy Aloysius; Nabil M.S. Amor; Reza Ardehali; Adriana Arneson; C. Scott Baker; Gareth Banks; Katherine Belov; Nigel C. Bennett; Peter Black; Daniel T. Blumstein; Eleanor K. Bors; Charles E. Breeze; Robert T. Brooke; Janine L. Brown; Gerald Carter; Alex Caulton; Julie M. Cavin; Lisa Chakrabarti; Ioulia Chatzistamou; Andreas S. Chavez; Hao Chen; Kaiyang Cheng; Priscila Chiavellini; Oi Wa Choi; Shannon Clarke; Joseph A. Cook; Lisa N. Cooper; Marie Laurence Cossette; Joanna Day; Joseph DeYoung; Stacy Dirocco; Christopher Dold; Jonathan L. Dunnum; Erin E. Ehmke; Candice K. Emmons; Stephan Emmrich; Ebru Erbay; Claire Erlacher-Reid; Chris G. Faulkes; Zhe Fei; Steven H. Ferguson; Carrie J. Finno; Jennifer E. Flower; Jean Michel Gaillard; Eva Garde; Livia Gerber; Vadim N. Gladyshev; Rodolfo G. Goya; Matthew J. Grant; Carla B. Green; M. Bradley Hanson; Daniel W. Hart; Martin Haulena; Kelsey Herrick; Andrew N. Hogan; Carolyn J. Hogg; Timothy A. Hore; Taosheng Huang; Juan Carlos Izpisua Belmonte; Anna J. Jasinska; Gareth Jones; Eve Jourdain; Olga Kashpur; Harold Katcher; Etsuko Katsumata; Vimala Kaza; Hippokratis Kiaris; Michael S. Kobor; Pawel Kordowitzki; William R. Koski; Michael Krötzen; Soo Bin Kwon; Brenda Larison; Sang Goo Lee; Marianne Lehmann; Jean François Lema tre; Andrew J. Levine; Xinmin Li; Cun Li; Andrea R. Lim; David T.S. Lin; Dana M. Lindemann; Schuyler W. Liphardt; Thomas J. Little; Nicholas Macoretta; Dewey Maddox; Craig O. Matkin; Julie A. Mattison; Matthew McClure; June Mergl; Jennifer J. Meudt; Gisele A. Montano; Khyobeni Mozhui; Jason Munshi-South; William J. Murphy; Asieh Naderi; Martina Nagy; Pritika Narayan; Peter W. Nathanielsz; Ngoc B. Nguyen; Christof Niehrs; Batsaikhan Nyamsuren; Justine K. O'Brien; Perrie O.Tierney Ginn; Duncan T. Odom; Alexander G. Ophir; Steve Osborn; Elaine A. Ostrander; Kim M. Parsons; Kimberly C. Paul; Amy B. Pedersen; Matteo Pellegrini; Katharina J. Peters; Jessica L. Petersen; Darren W. Pietersen; Gabriela M. Pinho; Jocelyn Plassais; Jesse R. Poganik; Natalia A. Prado; Pradeep Reddy; Benjamin Rey; Beate R. Ritz; Jooke Robbins; Magdalena Rodriguez; Jennifer Russell; Elena Rydkina; Lindsay L. Sailer; Adam B. Salmon; Akshay Sanghavi; Kyle M. Schachtschneider; Dennis Schmitt; Todd Schmitt; Lars Schomacher; Lawrence B. Schook; Karen E. Sears; Ashley W. Seifert; Aaron B.A. Shafer; Anastasia V. Shindyapina; Melanie Simmons; Kavita Singh; Ishani Sinha; Jesse Slone; Russel G. Snell; Elham Soltanmohammadi; Matthew L. Spangler; Maria Spriggs; Lydia Staggs; Nancy Stedman; Karen J. Steinman; Donald T. Stewart; Victoria J. Sugrue; Balazs Szladovits; Joseph S. Takahashi; Masaki Takasugi; Emma C. Teeling; Michael J. Thompson; Bill Van Bonn; Sonja C. Vernes; Diego Villar; Harry V. Vinters; Ha Vu; Mary C. Wallingford; Nan Wang; Gerald S. Wilkinson; Robert W. Williams; Qi Yan; Mingjia Yao; Brent G. Young; Bohan Zhang; Zhihui Zhang; Yang Zhao; Peng Zhao; Wanding Zhou; Joseph A. Zoller; Jason Ernst; Andrei Seluanov; Vera Gorbunova; X. William Yang; Ken Raj; Steve Horvath

doi:10.1126/science.abq5693

DNA methylation networks underlying mammalian traits

Amin Haghani, Caesar Z. Li, Todd R. Robeck, Joshua Zhang, Ake T. Lu, Julia Ablaeva, Victoria A. Acosta-Rodríguez, Danielle M. Adams, Abdulaziz N. Alagaili, Javier Almunia, Ajoy Aloysius, Nabil M.S. Amor, Reza Ardehali, Adriana Arneson, C. Scott Baker, Gareth Banks, Katherine Belov, Nigel C. Bennett, Peter Black, Daniel T. BlumsteinEleanor K. Bors, Charles E. Breeze, Robert T. Brooke, Janine L. Brown, Gerald Carter, Alex Caulton, Julie M. Cavin, Lisa Chakrabarti, Ioulia Chatzistamou, Andreas S. Chavez, Hao Chen, Kaiyang Cheng, Priscila Chiavellini, Oi Wa Choi, Shannon Clarke, Joseph A. Cook, Lisa N. Cooper, Marie Laurence Cossette, Joanna Day, Joseph DeYoung, Stacy Dirocco, Christopher Dold, Jonathan L. Dunnum, Erin E. Ehmke, Candice K. Emmons, Stephan Emmrich, Ebru Erbay, Claire Erlacher-Reid, Chris G. Faulkes, Zhe Fei, Steven H. Ferguson, Carrie J. Finno, Jennifer E. Flower, Jean Michel Gaillard, Eva Garde, Livia Gerber, Vadim N. Gladyshev, Rodolfo G. Goya, Matthew J. Grant, Carla B. Green, M. Bradley Hanson, Daniel W. Hart, Martin Haulena, Kelsey Herrick, Andrew N. Hogan, Carolyn J. Hogg, Timothy A. Hore, Taosheng Huang, Juan Carlos Izpisua Belmonte, Anna J. Jasinska, Gareth Jones, Eve Jourdain, Olga Kashpur, Harold Katcher, Etsuko Katsumata, Vimala Kaza, Hippokratis Kiaris, Michael S. Kobor, Pawel Kordowitzki, William R. Koski, Michael Krötzen, Soo Bin Kwon, Brenda Larison, Sang Goo Lee, Marianne Lehmann, Jean François Lema tre, Andrew J. Levine, Xinmin Li, Cun Li, Andrea R. Lim, David T.S. Lin, Dana M. Lindemann, Schuyler W. Liphardt, Thomas J. Little, Nicholas Macoretta, Dewey Maddox, Craig O. Matkin, Julie A. Mattison, Matthew McClure, June Mergl, Jennifer J. Meudt, Gisele A. Montano, Khyobeni Mozhui, Jason Munshi-South, William J. Murphy, Asieh Naderi, Martina Nagy, Pritika Narayan, Peter W. Nathanielsz, Ngoc B. Nguyen, Christof Niehrs, Batsaikhan Nyamsuren, Justine K. O'Brien, Perrie O.Tierney Ginn, Duncan T. Odom, Alexander G. Ophir, Steve Osborn, Elaine A. Ostrander, Kim M. Parsons, Kimberly C. Paul, Amy B. Pedersen, Matteo Pellegrini, Katharina J. Peters, Jessica L. Petersen, Darren W. Pietersen, Gabriela M. Pinho, Jocelyn Plassais, Jesse R. Poganik, Natalia A. Prado, Pradeep Reddy, Benjamin Rey, Beate R. Ritz, Jooke Robbins, Magdalena Rodriguez, Jennifer Russell, Elena Rydkina, Lindsay L. Sailer, Adam B. Salmon, Akshay Sanghavi, Kyle M. Schachtschneider, Dennis Schmitt, Todd Schmitt, Lars Schomacher, Lawrence B. Schook, Karen E. Sears, Ashley W. Seifert, Aaron B.A. Shafer, Anastasia V. Shindyapina, Melanie Simmons, Kavita Singh, Ishani Sinha, Jesse Slone, Russel G. Snell, Elham Soltanmohammadi, Matthew L. Spangler, Maria Spriggs, Lydia Staggs, Nancy Stedman, Karen J. Steinman, Donald T. Stewart, Victoria J. Sugrue, Balazs Szladovits, Joseph S. Takahashi, Masaki Takasugi, Emma C. Teeling, Michael J. Thompson, Bill Van Bonn, Sonja C. Vernes, Diego Villar, Harry V. Vinters, Ha Vu, Mary C. Wallingford, Nan Wang, Gerald S. Wilkinson, Robert W. Williams, Qi Yan, Mingjia Yao, Brent G. Young, Bohan Zhang, Zhihui Zhang, Yang Zhao, Peng Zhao, Wanding Zhou, Joseph A. Zoller, Jason Ernst, Andrei Seluanov, Vera Gorbunova, X. William Yang, Ken Raj, Steve Horvath

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Using DNA methylation profiles (n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.

Original language	English (US)
Article number	eabq5693
Journal	Science
Volume	381
Issue number	6658
DOIs	https://doi.org/10.1126/science.abq5693
State	Published - Aug 1 2023
Externally published	Yes

ASJC Scopus subject areas

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10.1126/science.abq5693

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Haghani, A., Li, C. Z., Robeck, T. R., Zhang, J., Lu, A. T., Ablaeva, J., Acosta-Rodríguez, V. A., Adams, D. M., Alagaili, A. N., Almunia, J., Aloysius, A., Amor, N. M. S., Ardehali, R., Arneson, A., Scott Baker, C., Banks, G., Belov, K., Bennett, N. C., Black, P., ... Horvath, S. (2023). DNA methylation networks underlying mammalian traits. Science, 381(6658), Article eabq5693. https://doi.org/10.1126/science.abq5693

Haghani, A, Li, CZ, Robeck, TR, Zhang, J, Lu, AT, Ablaeva, J, Acosta-Rodríguez, VA, Adams, DM, Alagaili, AN, Almunia, J, Aloysius, A, Amor, NMS, Ardehali, R, Arneson, A, Scott Baker, C, Banks, G, Belov, K, Bennett, NC, Black, P, Blumstein, DT, Bors, EK, Breeze, CE, Brooke, RT, Brown, JL, Carter, G, Caulton, A, Cavin, JM, Chakrabarti, L, Chatzistamou, I, Chavez, AS, Chen, H, Cheng, K, Chiavellini, P, Choi, OW, Clarke, S, Cook, JA, Cooper, LN, Cossette, ML, Day, J, DeYoung, J, Dirocco, S, Dold, C, Dunnum, JL, Ehmke, EE, Emmons, CK, Emmrich, S, Erbay, E, Erlacher-Reid, C, Faulkes, CG, Fei, Z, Ferguson, SH, Finno, CJ, Flower, JE, Gaillard, JM, Garde, E, Gerber, L, Gladyshev, VN, Goya, RG, Grant, MJ, Green, CB, Bradley Hanson, M, Hart, DW, Haulena, M, Herrick, K, Hogan, AN, Hogg, CJ, Hore, TA, Huang, T, Belmonte, JCI, Jasinska, AJ, Jones, G, Jourdain, E, Kashpur, O, Katcher, H, Katsumata, E, Kaza, V, Kiaris, H, Kobor, MS, Kordowitzki, P, Koski, WR, Krötzen, M, Kwon, SB, Larison, B, Lee, SG, Lehmann, M, Lema tre, JF, Levine, AJ, Li, X, Li, C, Lim, AR, Lin, DTS, Lindemann, DM, Liphardt, SW, Little, TJ, Macoretta, N, Maddox, D, Matkin, CO, Mattison, JA, McClure, M, Mergl, J, Meudt, JJ, Montano, GA, Mozhui, K, Munshi-South, J, Murphy, WJ, Naderi, A, Nagy, M, Narayan, P, Nathanielsz, PW, Nguyen, NB, Niehrs, C, Nyamsuren, B, O'Brien, JK, Ginn, POT, Odom, DT, Ophir, AG, Osborn, S, Ostrander, EA, Parsons, KM, Paul, KC, Pedersen, AB, Pellegrini, M, Peters, KJ, Petersen, JL, Pietersen, DW, Pinho, GM, Plassais, J, Poganik, JR, Prado, NA, Reddy, P, Rey, B, Ritz, BR, Robbins, J, Rodriguez, M, Russell, J, Rydkina, E, Sailer, LL, Salmon, AB, Sanghavi, A, Schachtschneider, KM, Schmitt, D, Schmitt, T, Schomacher, L, Schook, LB, Sears, KE, Seifert, AW, Shafer, ABA, Shindyapina, AV, Simmons, M, Singh, K, Sinha, I, Slone, J, Snell, RG, Soltanmohammadi, E, Spangler, ML, Spriggs, M, Staggs, L, Stedman, N, Steinman, KJ, Stewart, DT, Sugrue, VJ, Szladovits, B, Takahashi, JS, Takasugi, M, Teeling, EC, Thompson, MJ, Bonn, BV, Vernes, SC, Villar, D, Vinters, HV, Vu, H, Wallingford, MC, Wang, N, Wilkinson, GS, Williams, RW, Yan, Q, Yao, M, Young, BG, Zhang, B, Zhang, Z, Zhao, Y, Zhao, P, Zhou, W, Zoller, JA, Ernst, J, Seluanov, A, Gorbunova, V, William Yang, X, Raj, K & Horvath, S 2023, 'DNA methylation networks underlying mammalian traits', Science, vol. 381, no. 6658, eabq5693. https://doi.org/10.1126/science.abq5693

@article{83da0affcdd243f98242af3d8723a29f,

title = "DNA methylation networks underlying mammalian traits",

abstract = "Using DNA methylation profiles (n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.",

author = "Amin Haghani and Li, {Caesar Z.} and Robeck, {Todd R.} and Joshua Zhang and Lu, {Ake T.} and Julia Ablaeva and Acosta-Rodr{\'i}guez, {Victoria A.} and Adams, {Danielle M.} and Alagaili, {Abdulaziz N.} and Javier Almunia and Ajoy Aloysius and Amor, {Nabil M.S.} and Reza Ardehali and Adriana Arneson and {Scott Baker}, C. and Gareth Banks and Katherine Belov and Bennett, {Nigel C.} and Peter Black and Blumstein, {Daniel T.} and Bors, {Eleanor K.} and Breeze, {Charles E.} and Brooke, {Robert T.} and Brown, {Janine L.} and Gerald Carter and Alex Caulton and Cavin, {Julie M.} and Lisa Chakrabarti and Ioulia Chatzistamou and Chavez, {Andreas S.} and Hao Chen and Kaiyang Cheng and Priscila Chiavellini and Choi, {Oi Wa} and Shannon Clarke and Cook, {Joseph A.} and Cooper, {Lisa N.} and Cossette, {Marie Laurence} and Joanna Day and Joseph DeYoung and Stacy Dirocco and Christopher Dold and Dunnum, {Jonathan L.} and Ehmke, {Erin E.} and Emmons, {Candice K.} and Stephan Emmrich and Ebru Erbay and Claire Erlacher-Reid and Faulkes, {Chris G.} and Zhe Fei and Ferguson, {Steven H.} and Finno, {Carrie J.} and Flower, {Jennifer E.} and Gaillard, {Jean Michel} and Eva Garde and Livia Gerber and Gladyshev, {Vadim N.} and Goya, {Rodolfo G.} and Grant, {Matthew J.} and Green, {Carla B.} and {Bradley Hanson}, M. and Hart, {Daniel W.} and Martin Haulena and Kelsey Herrick and Hogan, {Andrew N.} and Hogg, {Carolyn J.} and Hore, {Timothy A.} and Taosheng Huang and Belmonte, {Juan Carlos Izpisua} and Jasinska, {Anna J.} and Gareth Jones and Eve Jourdain and Olga Kashpur and Harold Katcher and Etsuko Katsumata and Vimala Kaza and Hippokratis Kiaris and Kobor, {Michael S.} and Pawel Kordowitzki and Koski, {William R.} and Michael Kr{\"o}tzen and Kwon, {Soo Bin} and Brenda Larison and Lee, {Sang Goo} and Marianne Lehmann and {Lema tre}, {Jean Fran{\c c}ois} and Levine, {Andrew J.} and Xinmin Li and Cun Li and Lim, {Andrea R.} and Lin, {David T.S.} and Lindemann, {Dana M.} and Liphardt, {Schuyler W.} and Little, {Thomas J.} and Nicholas Macoretta and Dewey Maddox and Matkin, {Craig O.} and Mattison, {Julie A.} and Matthew McClure and June Mergl and Meudt, {Jennifer J.} and Montano, {Gisele A.} and Khyobeni Mozhui and Jason Munshi-South and Murphy, {William J.} and Asieh Naderi and Martina Nagy and Pritika Narayan and Nathanielsz, {Peter W.} and Nguyen, {Ngoc B.} and Christof Niehrs and Batsaikhan Nyamsuren and O'Brien, {Justine K.} and Ginn, {Perrie O.Tierney} and Odom, {Duncan T.} and Ophir, {Alexander G.} and Steve Osborn and Ostrander, {Elaine A.} and Parsons, {Kim M.} and Paul, {Kimberly C.} and Pedersen, {Amy B.} and Matteo Pellegrini and Peters, {Katharina J.} and Petersen, {Jessica L.} and Pietersen, {Darren W.} and Pinho, {Gabriela M.} and Jocelyn Plassais and Poganik, {Jesse R.} and Prado, {Natalia A.} and Pradeep Reddy and Benjamin Rey and Ritz, {Beate R.} and Jooke Robbins and Magdalena Rodriguez and Jennifer Russell and Elena Rydkina and Sailer, {Lindsay L.} and Salmon, {Adam B.} and Akshay Sanghavi and Schachtschneider, {Kyle M.} and Dennis Schmitt and Todd Schmitt and Lars Schomacher and Schook, {Lawrence B.} and Sears, {Karen E.} and Seifert, {Ashley W.} and Shafer, {Aaron B.A.} and Shindyapina, {Anastasia V.} and Melanie Simmons and Kavita Singh and Ishani Sinha and Jesse Slone and Snell, {Russel G.} and Elham Soltanmohammadi and Spangler, {Matthew L.} and Maria Spriggs and Lydia Staggs and Nancy Stedman and Steinman, {Karen J.} and Stewart, {Donald T.} and Sugrue, {Victoria J.} and Balazs Szladovits and Takahashi, {Joseph S.} and Masaki Takasugi and Teeling, {Emma C.} and Thompson, {Michael J.} and Bonn, {Bill Van} and Vernes, {Sonja C.} and Diego Villar and Vinters, {Harry V.} and Ha Vu and Wallingford, {Mary C.} and Nan Wang and Wilkinson, {Gerald S.} and Williams, {Robert W.} and Qi Yan and Mingjia Yao and Young, {Brent G.} and Bohan Zhang and Zhihui Zhang and Yang Zhao and Peng Zhao and Wanding Zhou and Zoller, {Joseph A.} and Jason Ernst and Andrei Seluanov and Vera Gorbunova and {William Yang}, X. and Ken Raj and Steve Horvath",

year = "2023",

month = aug,

day = "1",

doi = "10.1126/science.abq5693",

language = "English (US)",

volume = "381",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6658",

}

TY - JOUR

T1 - DNA methylation networks underlying mammalian traits

AU - Haghani, Amin

AU - Li, Caesar Z.

AU - Robeck, Todd R.

AU - Zhang, Joshua

AU - Lu, Ake T.

AU - Ablaeva, Julia

AU - Acosta-Rodríguez, Victoria A.

AU - Adams, Danielle M.

AU - Alagaili, Abdulaziz N.

AU - Almunia, Javier

AU - Aloysius, Ajoy

AU - Amor, Nabil M.S.

AU - Ardehali, Reza

AU - Arneson, Adriana

AU - Scott Baker, C.

AU - Banks, Gareth

AU - Belov, Katherine

AU - Bennett, Nigel C.

AU - Black, Peter

AU - Blumstein, Daniel T.

AU - Bors, Eleanor K.

AU - Breeze, Charles E.

AU - Brooke, Robert T.

AU - Brown, Janine L.

AU - Carter, Gerald

AU - Caulton, Alex

AU - Cavin, Julie M.

AU - Chakrabarti, Lisa

AU - Chatzistamou, Ioulia

AU - Chavez, Andreas S.

AU - Chen, Hao

AU - Cheng, Kaiyang

AU - Chiavellini, Priscila

AU - Choi, Oi Wa

AU - Clarke, Shannon

AU - Cook, Joseph A.

AU - Cooper, Lisa N.

AU - Cossette, Marie Laurence

AU - Day, Joanna

AU - DeYoung, Joseph

AU - Dirocco, Stacy

AU - Dold, Christopher

AU - Dunnum, Jonathan L.

AU - Ehmke, Erin E.

AU - Emmons, Candice K.

AU - Emmrich, Stephan

AU - Erbay, Ebru

AU - Erlacher-Reid, Claire

AU - Faulkes, Chris G.

AU - Fei, Zhe

AU - Ferguson, Steven H.

AU - Finno, Carrie J.

AU - Flower, Jennifer E.

AU - Gaillard, Jean Michel

AU - Garde, Eva

AU - Gerber, Livia

AU - Gladyshev, Vadim N.

AU - Goya, Rodolfo G.

AU - Grant, Matthew J.

AU - Green, Carla B.

AU - Bradley Hanson, M.

AU - Hart, Daniel W.

AU - Haulena, Martin

AU - Herrick, Kelsey

AU - Hogan, Andrew N.

AU - Hogg, Carolyn J.

AU - Hore, Timothy A.

AU - Huang, Taosheng

AU - Belmonte, Juan Carlos Izpisua

AU - Jasinska, Anna J.

AU - Jones, Gareth

AU - Jourdain, Eve

AU - Kashpur, Olga

AU - Katcher, Harold

AU - Katsumata, Etsuko

AU - Kaza, Vimala

AU - Kiaris, Hippokratis

AU - Kobor, Michael S.

AU - Kordowitzki, Pawel

AU - Koski, William R.

AU - Krötzen, Michael

AU - Kwon, Soo Bin

AU - Larison, Brenda

AU - Lee, Sang Goo

AU - Lehmann, Marianne

AU - Lema tre, Jean François

AU - Levine, Andrew J.

AU - Li, Xinmin

AU - Li, Cun

AU - Lim, Andrea R.

AU - Lin, David T.S.

AU - Lindemann, Dana M.

AU - Liphardt, Schuyler W.

AU - Little, Thomas J.

AU - Macoretta, Nicholas

AU - Maddox, Dewey

AU - Matkin, Craig O.

AU - Mattison, Julie A.

AU - McClure, Matthew

AU - Mergl, June

AU - Meudt, Jennifer J.

AU - Montano, Gisele A.

AU - Mozhui, Khyobeni

AU - Munshi-South, Jason

AU - Murphy, William J.

AU - Naderi, Asieh

AU - Nagy, Martina

AU - Narayan, Pritika

AU - Nathanielsz, Peter W.

AU - Nguyen, Ngoc B.

AU - Niehrs, Christof

AU - Nyamsuren, Batsaikhan

AU - O'Brien, Justine K.

AU - Ginn, Perrie O.Tierney

AU - Odom, Duncan T.

AU - Ophir, Alexander G.

AU - Osborn, Steve

AU - Ostrander, Elaine A.

AU - Parsons, Kim M.

AU - Paul, Kimberly C.

AU - Pedersen, Amy B.

AU - Pellegrini, Matteo

AU - Peters, Katharina J.

AU - Petersen, Jessica L.

AU - Pietersen, Darren W.

AU - Pinho, Gabriela M.

AU - Plassais, Jocelyn

AU - Poganik, Jesse R.

AU - Prado, Natalia A.

AU - Reddy, Pradeep

AU - Rey, Benjamin

AU - Ritz, Beate R.

AU - Robbins, Jooke

AU - Rodriguez, Magdalena

AU - Russell, Jennifer

AU - Rydkina, Elena

AU - Sailer, Lindsay L.

AU - Salmon, Adam B.

AU - Sanghavi, Akshay

AU - Schachtschneider, Kyle M.

AU - Schmitt, Dennis

AU - Schmitt, Todd

AU - Schomacher, Lars

AU - Schook, Lawrence B.

AU - Sears, Karen E.

AU - Seifert, Ashley W.

AU - Shafer, Aaron B.A.

AU - Shindyapina, Anastasia V.

AU - Simmons, Melanie

AU - Singh, Kavita

AU - Sinha, Ishani

AU - Slone, Jesse

AU - Snell, Russel G.

AU - Soltanmohammadi, Elham

AU - Spangler, Matthew L.

AU - Spriggs, Maria

AU - Staggs, Lydia

AU - Stedman, Nancy

AU - Steinman, Karen J.

AU - Stewart, Donald T.

AU - Sugrue, Victoria J.

AU - Szladovits, Balazs

AU - Takahashi, Joseph S.

AU - Takasugi, Masaki

AU - Teeling, Emma C.

AU - Thompson, Michael J.

AU - Bonn, Bill Van

AU - Vernes, Sonja C.

AU - Villar, Diego

AU - Vinters, Harry V.

AU - Vu, Ha

AU - Wallingford, Mary C.

AU - Wang, Nan

AU - Wilkinson, Gerald S.

AU - Williams, Robert W.

AU - Yan, Qi

AU - Yao, Mingjia

AU - Young, Brent G.

AU - Zhang, Bohan

AU - Zhang, Zhihui

AU - Zhao, Yang

AU - Zhao, Peng

AU - Zhou, Wanding

AU - Zoller, Joseph A.

AU - Ernst, Jason

AU - Seluanov, Andrei

AU - Gorbunova, Vera

AU - William Yang, X.

AU - Raj, Ken

AU - Horvath, Steve

PY - 2023/8/1

Y1 - 2023/8/1

N2 - Using DNA methylation profiles (n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.

AB - Using DNA methylation profiles (n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.

UR - http://www.scopus.com/inward/record.url?scp=85167657141&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85167657141&partnerID=8YFLogxK

U2 - 10.1126/science.abq5693

DO - 10.1126/science.abq5693

M3 - Article

C2 - 37561875

AN - SCOPUS:85167657141

SN - 0036-8075

VL - 381

JO - Science

JF - Science

IS - 6658

M1 - eabq5693

ER -

DNA methylation networks underlying mammalian traits

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