---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '22720'
abstract:
- lang: eng
  text: Circadian clocks underlie daily rhythms in physiology by coordinating temporal
    patterns of gene expression and protein function throughout the body. At the core
    of this system in mammals is CLOCK/BMAL1, a ubiquitously expressed heterodimeric
    transcription factor complex that orchestrates tissue-specific circadian gene
    expression. The basis for this specificity remains unclear, but tissue-specific
    interactions at chromatin could provide one. Here we used chromatin immunoprecipitation
    coupled to mass spectrometry to map CLOCK/BMAL1-associated protein complexes on
    chromatin in mouse liver, kidney and lung. We detected 1,510 associated proteins,
    most of which were tissue-specific and not explained by protein abundance. Among
    these, we identified the homeodomain transcription factors PROX1, HNF1B and HOXA5
    as tissue-enriched interactors that bind BMAL1, co-occupy most BMAL1 genomic sites
    and establish organ-restricted circadian transcription. Our findings demonstrate
    that tissue-specific transcription factors confer cellular identity on the core
    clock, thereby contributing to organ-specific patterns of rhythmic gene expression.
acknowledgement: We thank all members of the Robles’ group for critical comments on
  and edits to this paper. We thank S. Kay for providing dihXY HCC cell lines and
  D. Firsov and Y. Bignon for mouse BMAL1-knockout (KO) kidney tissues. This work
  was supported by the German Research Foundation (DFG) project no. 213249687—SFB
  1064 and RO 5675/1-1 to M.S.R., F.A. and L.A.H. M.S.R was also supported by DFG
  INST 86/1800-1 FUGG and LMU Munich’s Institutional Strategy LMU excellent within
  the framework of the German Excellence Initiative. J.S.M. was supported by US National
  Institutes of Health grant nos. R01GM145737 and R01DK128133. A.K.M. was supported
  by an ERC grant ‘ChromaChrono’ 101162145. Open access funding provided by Ludwig-Maximilians-Universität
  München.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Fatih
  full_name: Aygenli, Fatih
  last_name: Aygenli
- first_name: Lukas A.
  full_name: Huschet, Lukas A.
  last_name: Huschet
- first_name: Tanja
  full_name: Popp, Tanja
  last_name: Popp
- first_name: Andrea
  full_name: Ribeiro, Andrea
  last_name: Ribeiro
- first_name: Darina
  full_name: Barkhatova, Darina
  id: db547c8c-329f-11ee-a353-cde802618f9e
  last_name: Barkhatova
  orcid: 0000-0002-0062-2817
- first_name: Céline
  full_name: Jouffe, Céline
  last_name: Jouffe
- first_name: Ricardo
  full_name: Trozzo, Ricardo
  last_name: Trozzo
- first_name: Jerome S.
  full_name: Menet, Jerome S.
  last_name: Menet
- first_name: Roland
  full_name: Rad, Roland
  last_name: Rad
- first_name: Kenneth A.
  full_name: Dyar, Kenneth A.
  last_name: Dyar
- first_name: Maciej
  full_name: Lech, Maciej
  last_name: Lech
- first_name: Tobias
  full_name: Straub, Tobias
  last_name: Straub
- first_name: Alicia
  full_name: Michael, Alicia
  id: 6437c950-2a03-11ee-914d-d6476dd7b75c
  last_name: Michael
  orcid: 0000-0002-6080-839X
- first_name: Maria S.
  full_name: Robles, Maria S.
  last_name: Robles
citation:
  ama: Aygenli F, Huschet LA, Popp T, et al. CLOCK/BMAL1 interactome uncovers homeodomain
    factors as tissue regulators. <i>Nature Cell Biology</i>. 2026. doi:<a href="https://doi.org/10.1038/s41556-026-02041-4">10.1038/s41556-026-02041-4</a>
  apa: Aygenli, F., Huschet, L. A., Popp, T., Ribeiro, A., Barkhatova, D., Jouffe,
    C., … Robles, M. S. (2026). CLOCK/BMAL1 interactome uncovers homeodomain factors
    as tissue regulators. <i>Nature Cell Biology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41556-026-02041-4">https://doi.org/10.1038/s41556-026-02041-4</a>
  chicago: Aygenli, Fatih, Lukas A. Huschet, Tanja Popp, Andrea Ribeiro, Darina Barkhatova,
    Céline Jouffe, Ricardo Trozzo, et al. “CLOCK/BMAL1 Interactome Uncovers Homeodomain
    Factors as Tissue Regulators.” <i>Nature Cell Biology</i>. Springer Nature, 2026.
    <a href="https://doi.org/10.1038/s41556-026-02041-4">https://doi.org/10.1038/s41556-026-02041-4</a>.
  ieee: F. Aygenli <i>et al.</i>, “CLOCK/BMAL1 interactome uncovers homeodomain factors
    as tissue regulators,” <i>Nature Cell Biology</i>. Springer Nature, 2026.
  ista: Aygenli F, Huschet LA, Popp T, Ribeiro A, Barkhatova D, Jouffe C, Trozzo R,
    Menet JS, Rad R, Dyar KA, Lech M, Straub T, Michael AK, Robles MS. 2026. CLOCK/BMAL1
    interactome uncovers homeodomain factors as tissue regulators. Nature Cell Biology.
  mla: Aygenli, Fatih, et al. “CLOCK/BMAL1 Interactome Uncovers Homeodomain Factors
    as Tissue Regulators.” <i>Nature Cell Biology</i>, Springer Nature, 2026, doi:<a
    href="https://doi.org/10.1038/s41556-026-02041-4">10.1038/s41556-026-02041-4</a>.
  short: F. Aygenli, L.A. Huschet, T. Popp, A. Ribeiro, D. Barkhatova, C. Jouffe,
    R. Trozzo, J.S. Menet, R. Rad, K.A. Dyar, M. Lech, T. Straub, A.K. Michael, M.S.
    Robles, Nature Cell Biology (2026).
das_tickbox: '1'
dataavailabilitystatement: Proteomics data have been deposited to the ProteomeXchange
  Consortium via the PRIDE64 partner repository with the dataset identifiers PXD062751
  and PXD077567. RNA-seq data are available in the European Nucleotide Archive (ENA)
  under accession no. PRJEB93884, and ChIP–seq data at the Gene Expression Omnibus
  (GEO) under accession no. GSE302237. AlphaFold 3 interaction prediction parameters
  can be provided during the revision process on editorial and/or review request.
  Source data are provided with this paper.
date_created: 2026-08-16T22:01:44Z
date_published: 2026-08-06T00:00:00Z
date_updated: 2026-08-18T08:03:22Z
day: '06'
ddc:
- '570'
department:
- _id: GradSch
- _id: AlMi
doi: 10.1038/s41556-026-02041-4
external_id:
  pmid:
  - '42562924'
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41556-026-02041-4
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 9136c684-16d5-11f0-9cad-91c0177b365f
  grant_number: '101162145'
  name: Circadian structural transitions of chromatin
publication: Nature Cell Biology
publication_identifier:
  eissn:
  - 1476-4679
  issn:
  - 1465-7392
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...