The BRCT-Domain Containing Protein PTIP Links PAX2 to a Histone H3, Lysine 4 Methyltransferase Complex
Open accessAbstract
The MLL family of histone methyltransferases maintains active chromatin domains by methylating histone H3 on lysine 4 (H3K4). How MLL complexes recognize specific chromatin domains in a temporal and tissue-specific manner remains unclear. We show that the DNA-binding protein PAX2 promotes assembly of an H3K4 methyltransferase complex through the ubiquitously expressed nuclear factor PTIP (pax transcription activation domain interacting protein). PTIP copurifies with ALR, MLL3, and other components of a histone methyltransferase complex. PTIP promotes assembly of the ALR complex and H3K4 methylation at a PAX2-binding DNA element. Without PTIP, Pax2 binds to this element but does not assemble the ALR complex. Embryonic lethal ptip-null mutants and conditional mutants both show reduced levels of methylated H3K4. Thus, PTIP bridges DNA-binding developmental regulators to histone methyltransferase-dependent epigenetic regulation.
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Some studies show that signalling-dependent and cell type-specific TFs are capable of recruiting MLL4 to establish H3K4me1 at enhancers.
“While some studies show that signalling-dependent and cell type-specific TFs are capable of recruiting MLL4 to establish H3K4me1 at enhancers44–47, whether HNF4A has this function is not known.”
From HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements (2024) · cites this paper as [45]
Cites
Regulation of chromatin structure by site-specific histone H3 methyltransferases
Rea, S., Eisenhaber, F., O'Carroll, D., Strahl, B. D., Sun, Z.-W., Schmid, M., Opravil, S., Mechtler, K., Ponting, C. P., Allis, C. D., et al. (2000) · Nature · doi:10.1038/35020506 · Cited by 2,845 · cited 2× · see citing works
“Methylation of H3K9 by the mammalian HMT Suv39h (Rea et al., 2000) correlates with silent chromatin (Litt et al., 2001), whereas actively expressed genes are enriched in di- (me2) and trimethylated (me3) histone H3K4 (Santos-Rosa et al., 2002).”
BackgroundStructure of the BRCT Repeats of BRCA1 Bound to a BACH1 Phosphopeptide
Shiozaki, E. N., Gu, L., Yan, N., & Shi, Y. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00238-2 · Cited by 174 · see citing works
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Shilatifard, A. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-051710-134100 · Cited by 1,091 · see citing works
Genetic, environmental, and epigenetic factors involved in CAKUT
Nicolaou, N., Renkema, K. Y., Bongers, E. M. H. F., Giles, R. H., & Knoers, N. V. A. M. (2015) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.140 · Cited by 344 · see citing works
The MLL3/4 H3K4 methyltransferase complex in establishing an active enhancer landscape
Wang, L.-H., Aberin, M. A. E., Wu, S., & Wang, S.-P. (2021) · Biochemical Society Transactions · doi:10.1042/bst20191164 · Cited by 53 · see citing works
HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements
Thakur, A., Park, K., Cullum, R., Fuglerud, B. M., Khoshnoodi, M., Drissler, S., Stephan, T. L., Lotto, J., Kim, D., Gonzalez, F. J., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-05835-0 · Cited by 10 · see citing works
Self-citation
- Authors
- Patel, S. R., Kim, D., Levitan, I., & Dressler, G. R.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Dressler, Gregory R.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 13
- Issue
- 4
- Pages
- 580-592
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC2100379
- OpenAlex
- W2015477868
- Cited by
- 249
- References
- 2
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 17 · 2023: 12 · 2022: 10 · 2021: 12 · 2020: 15 · 2019: 6 · 2018: 15 · 2017: 12 · 2016: 14 · 2015: 19 · 2014: 12 · 2013: 18 · 2012: 23
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Michigan
- National Institutes of Health (5p50dk039255-20)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK02803, P50-DK039255, R01DK073722, R01DK054740, DK073722, DK054740, K08DK002803, DK039255)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- PTIP, PAX2, H3K4 methylation, histone methyltransferase complex, MLL3, chromatin assembly, epigenetic regulation, developmental regulators, conditional knockout mice
- MeSH terms
- Histone Methyltransferases, Animals, Carrier Proteins, Cell Line, DNA-Binding Proteins, Histones, Humans, Lysine, Methylation, Nuclear Proteins, Protein Binding, Histone-Lysine N-Methyltransferase, Protein Methyltransferases, Protein Structure, Tertiary, Epigenesis, Genetic, Mice, PAX2 Transcription Factor, Gastrulation
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