The Epigenetic Faces of ULTRAPETALA1

Abstract

ULTRAPETALA1 (ULT1) is a versatile plant-exclusive protein, initially described as a trithorax group (TrxG) factor that regulates transcriptional activation and counteracts polycomb group (PcG) repressor function. As part of TrxG, ULT1 interacts with ARABIDOPSIS TRITHORAX1 (ATX1) to regulate H3K4me3 activation mark deposition. However, our recent studies indicate that ULT1 can also act independently of ATX1. Moreover, the ULT1 ability to interact with transcription factors (TFs) and PcG proteins indicates that it is a versatile protein with other roles. Therefore, in this work we revised recent information about the function of Arabidopsis ULT1 to understand the roles of ULT1 in plant development. Furthermore, we discuss the molecular mechanisms of ULT1, highlighting its epigenetic role, in which ULT1 seems to have characteristics of an epigenetic molecular switch that regulates repression and activation processes via TrxG and PcG complexes.

Full text

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REVIEW
published: 25 February 2021
doi: 10.3389/fpls.2021.637244
Edited by:
Gang Wu,
Zhejiang Agriculture and Forestry
University, China
Reviewed by:
Chris Helliwell,
Commonwealth Scientific
and Industrial Research Organisation
(CSIRO), Australia
Li Pu,
Chinese Academy of Agricultural
Sciences, China
*Correspondence:
María de la Paz Sanchez
mpsanchez@iecologia.unam.mx
Specialty section:
This article was submitted to
Plant Development and EvoDevo,
a section of the journal
Frontiers in Plant Science
Received: 03 December 2020
Accepted: 21 January 2021
Published: 25 February 2021
Citation:
Ornelas-Ayala D, Garay-Arroyo A,
García-Ponce B, R Álvarez-Buylla E
and Sanchez MP (2021) The
Epigenetic Faces of ULTRAPETALA1.
Front. Plant Sci. 12:637244.
doi: 10.3389/fpls.2021.637244
The Epigenetic Faces of
ULTRAPETALA1
Diego Ornelas-Ayala1, Adriana Garay-Arroyo1,2 , Berenice García-Ponce1,
Elena R. Álvarez-Buylla1,2 and María de la Paz Sanchez1*
1Laboratorio de Genética Molecular, Epigenética, Desarrollo y Evolución de Plantas, Instituto de Ecología, Universidad
Nacional Autónoma de México, 3er Circuito Ext. Junto a J. Botánico, Ciudad Universitaria, UNAM, Mexico City, Mexico,
2Centro de Ciencias de la Complejidad (C3), Universidad Nacional Autónoma de México, Mexico City, Mexico
ULTRAPETALA1 (ULT1) is a versatile plant-exclusive protein, initially described as a
trithorax group (TrxG) factor that regulates transcriptional activation and counteracts
polycomb group (PcG) repressor function. As part of TrxG, ULT1 interacts with
ARABIDOPSIS TRITHORAX1 (ATX1) to regulate H3K4me3 activation mark deposition.
However, our recent studies indicate that ULT1 can also act independently of ATX1.
Moreover, the ULT1 ability to interact with transcription factors (TFs) and PcG proteins
indicates that it is a versatile protein with other roles. Therefore, in this work we revised
recent information about the function of Arabidopsis ULT1 to understand the roles of
ULT1 in plant development. Furthermore, we discuss the molecular mechanisms of
ULT1, highlighting its epigenetic role, in which ULT1 seems to have characteristics of
an epigenetic molecular switch that regulates repression and activation processes via
TrxG and PcG complexes.
Keywords: ULTRAPETALA1, TrxG, PcG, ATX1, Molecular epigenetic switch, Arabidopsis
INTRODUCTION
In multicellular organisms, epigenetic regulation plays crucial roles for the correct deployment of
developmental programs and for the establishment of cell fates. Epigenetic mechanisms include
post-translational histone modifications (PHM) that modulate chromatin structure to regulate
gene expression. The trithorax group (TrxG) is an epigenetic protein complex able to regulate
transcriptional activation through trimethylation of lysine 4 and 36 of histone H3 (H3K4me3 and
H3K36me3) as well as other associated PHMs (Schuettengruber et al., 2011). TrxG proteins are
those that belong to complexes counteracting of polycomb group (PcG) repressive activity at the
same set of target genes (Grimaud et al., 2006); however, other proteins that act together with TrxG
on PcG or non-PcG target genes are also considered TrxG (Schuettengruber et al., 2007).
In plants, TrxG participates in different developmental processes from embryogenesis to floral
development, regulating gene expression of several transcription factors (TFs) involved in stem
cell maintenance, cell fate identity, and cell proliferation and differentiation (Sanchez et al.,
2015;Fletcher, 2017). The plant TrxG complex has been identified by homology to known TrxG
proteins in animals or by genetic characterization based on their ability to counteract PcG mutant
phenotypes (Fletcher, 2017). In this regard, SET histone methyltransferases (HMTs) of MLL and
SET families, COMPASS-like proteins such as WDR5, ASH2L and RBBP5, and ATP-dependent
chromatin-remodeling factors such as BRM, CHD and BPTF, have been described in plants
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(Avramova, 2009;Schuettengruber et al., 2011;Sanchez et al.,
2015) (Figure 1). In Arabidopsis thaliana (hereafter Arabidopsis),
the main HMTs of TrxG that catalyze the H3K4me3 mark
are the ARABIDOPSIS TRITHORAX1 (ATX1) and the
ARABIDOPSIS TRITHORAX-RELATED 3/SETDOMAIN
GROUP 2 (ATXR3/SDG2) (Alvarez-Venegas et al., 2003;Berr
et al., 2010;Guo et al., 2010;Chen et al., 2017), although until
now, only ATX1 has been found to form a complex within the
core of Arabidopsis COMPASS-like complex described (Jiang
et al., 2011). Interestingly, it has been reported that the plant
TrxG group includes a unique protein named ULTRAPETALA1
(ULT1) (Figure 1), whose structure differs from all TrxG
components reported in animals and yeast. ULT1 has been
defined as a TrxG factor by counteract PcG silencing and by
its physical interaction with ATX1 (Carles and Fletcher, 2009;
Pu et al., 2013). However, our recent study indicates that ULT1
can act independently of ATX1, in a tissue-specific fashion
(Ornelas-Ayala et al., 2020). Moreover, the interactions of
ULT1 with PcG proteins (Xu et al., 2018) suggest other roles
of ULT1 as well. Therefore, here we review recent information
on the structure of the ULT1 protein, its interactions with
other proteins, and its gene targets, as well as the phenotypic
analysis of loss-of-function mutants to understand the roles
of ULT1 in plant development. Furthermore, we discuss the
molecular mechanisms in which ULT1 is involved, as well
as its possible function as an epigenetic molecular switch
that regulates repression and activation processes via TrxG
and PcG complexes.
WHAT THE ULT1 STRUCTURE REVEALS
ABOUT ITS FUNCTION
In Arabidopsis, ULT1 has been described as a SAND (named
after Sp100, AIRE, NucP41/75, DEAF-1) domain protein that
FIGURE 1 | Factors of the TrxG complex. Different proteins of the TrxG animal
complex that are conserved in plants such as (i) ATP-dependent
chromatin-remodeling factors, (ii) SET domain-containing proteins that
catalyze histone methylation, and (iii) COMPASS-like proteins. It is noteworthy
that plant TrxG includes SAND-domain proteins that are not conserved in
animals. The list of names below of each TrxG component shows the proteins
described in Arabidopsis (green color) and their mammalian counterparts
(orange color).
also contains a B-box motif (Figure 2A), a motif that seems
to be important for protein-protein interaction (Torok and
Etkin, 2001;Carles et al., 2005;Khanna et al., 2009). In
the case of OsULT1 from Oryza sativa, it has been shown
that is important for its multimerization (Roy et al., 2019).
Meanwhile, the SAND domain has a DNA-binding function
(Bottomley et al., 2001), and it is conserved in plants and
animals in vast combinations with other protein domains on
the Viridiplantae and metazoan lineages. The Clorophyta lineage
contains a single-SAND domain protein RegA, whereas in the
Embryophyte lineage only ULT and ATX3 (ARABIDOPSIS
THRITHORAX3) proteins and its paralogs contain a SAND
domain (Kirk et al., 1999;Nedelcu, 2019). In ULT proteins,
the SAND domain is unique, whereas in ATX3, it appears in
combination with the SET-like and PHD domains (Nedelcu,
2019). The SAND domain in combination with other protein
domains has also been related to chromatin interactions and
transcriptional regulation. For instance, AIRE (Autoimmune
Regulator) is capable of interacting with chromatin through
its PHD domain. AIRE binds specifically unmethylated H3K4
residues and it is proposed that this binding is important
for its function as a transcriptional activator (Org et al.,
2008). Moreover, the AIRE protein can associate with DNA
transcriptional control elements and factors involved in pre-
mRNA processing (Abramson et al., 2010) and also can
be acetylated by the CBP (CREB Binding Protein) and the
p300 histone acetyltransferases to enhance its transactivation
activity (Saare et al., 2012). Therefore, the SAND domain is
a DNA-binding module characteristic of chromatin-dependent
transcriptional regulation. In fact, by in vitro assays, it has been
shown that the SAND domain of human DEAF-1 (Deformed
Epidermal Autoregulatory Factor-1) homolog recognizes the 50-
TTCG-30sequence (Bottomley et al., 2001). This sequence differs
from what has been reported in plants, where the SAND domain
of recombinant OsULT1, has affinity for the 50-GAGAG-30
sequence (Roy et al., 2019).
Most of the SAND domain proteins of the different
lineages are involved in developmental processes such as cell
proliferation, cell differentiation, tissue homeostasis and organ
formation (Nedelcu, 2019). For instance, in the multicellular
green alga Volvox carteri, RegA is involved in somatic
cell differentiation (Kirk et al., 1999), while the DEAF-1
protein is necessary for embryonic development in Drosophila
melanogaster (Veraksa et al., 2002), and its ortholog in mammals
is involved in breast epithelial cell differentiation (Barker
et al., 2008). In addition, AIRE is an important transcriptional
activator to regulate autoimmune processes in the thymus
(Abramson et al., 2010).
In plants, ULT1 functions have been described only for
Arabidopsis and rice (see below); however, several ULT1
sequences have been reported in other species. In this kingdom,
ULT1 seems to be a protein exclusive to Angiosperms, since
Gymnosperm, Lycophytes or Mosses lack sequences homologous
to ULT1. In angiosperms ULT1 is highly conserved in
different species of Eudicots, Monocotyledons, and even in
Amborellales, considered one of the most basal angiosperms
(Chase et al., 2016), the latter being closer to Eudicots than
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FIGURE 2 | ULTRAPETALA1 is conserved in different angiosperm species. (A) The SAND-domain and B-box motif of ULT1 from Arabidopsis thaliana and its
alignment with ULT1 from Oryza sativa. The asterisks show identical residues; colons (:) and periods (.) show residues with strongly and weakly similar properties,
respectively. The blue boxes show the SAND-domain and the red boxes represent the B-box consensus motif. (B) Phylogenetic analysis generated using the
neighbor-joining method based on the ULT1 protein sequence of selected plant species. Numbers at nodes represent bootstrap percentages based on 10,000
samplings. The scale bars represent 0.1 substitutions per site.
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to Monocotyledons (Figure 2B). The topology of neighbor-
joining phylogenetic analysis shows a clear clade distribution
according to plant orders, with the exception of Vitis vinifera
that is closer to Poales (Figure 2B). Evolutionary conservation
is also observed for Arabidopsis ULT2, a paralog of ULT1,
which conserved a similar protein structure that includes
the SAND domain (Carles et al., 2005). The high identity
of ULT1 proteins in these species predicts similar functions
among them.
THE ROLE OF ULT1 AS PART OF TrxG
EPIGENETIC COMPLEX
The first reports on ULT1 function were made by analyzing the
ULT1 loss and gain-of-function mutant plants (Fletcher, 2001;
Carles et al., 2004, 2005;Carles and Fletcher, 2009). Indeed, loss of
function of ULT1 delays differentiation and increases shoot and
floral meristem size, producing extra-floral organs such as sepals
and petals, hence the name ULTRAPETALA (Fletcher, 2001;
Carles et al., 2004). In the shoot apical meristem (SAM), ULT1
positively regulates the expression of APETALA3 (AP3) and
AGAMOUS (AG) (Figure 3A), two genes of the ABC flower
organ identity model (Carles and Fletcher, 2009). However,
ULT1 was also described as a negative regulator of WUSCHEL
(WUS) expression (Figure 3B), a TF that maintains stem cells
in the meristems and must be repressed in order to establish
floral determinacy (Carles et al., 2004). Therefore, these reports
describe ULT1 as a putative transcriptional regulator, involved in
shoot meristem maintenance and floral meristem differentiation
and determinacy. Nevertheless, the opposite regulation between
ULT1 and CURLY LEAF (CLF), an HMT of the Arabidopsis
PcG repressive complex, observed in some vegetative and
reproductive organs (Carles and Fletcher, 2009), as well as the
antagonistic function of ULT1 with EMBRYONIC FLOWER1
(EMF1), another PcG component (Pu et al., 2013), together
with the ability of ULT1 to physically interact with the ATX1,
have led to propose ULT1 as a TrxG factor with coactivator
FIGURE 3 | Different roles of ULT1 during Arabidopsis development. (A) ULT1 interacts with ATX1 to counteract PcG functions in the SAM. (B) ULT1 interacts with
UIF1 to repress the WUS expression in the SAM. ULT1 may also act with KAN1 to regulate the apical/basal patterning of the gynoecium and it can function
antagonistically with KAN1 to regulate the adaxial/abaxial patterning of the gynoecium. (C) ULT1 regulates auxin response, the QC cell division rate, and the
columella stem cells (CSC) differentiation to maintain root SCN, independently of ATX1. (D) ULT1 interacts with EMF1 to keep the repression of seed development
genes by maintaining the H3K27me3 marks. The green and blue boxes represent H3K4me3 and H3K27me3 marks, respectively.
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properties of some genes related to the SAM development
(Carles and Fletcher, 2009).
Furthermore, despite the lack of HMT activity of ULT1, it
has been suggested that ult1 mutant plants have lower levels of
H3K4me3 marks on AG and AP3 genes, which are associated
with an increase of H3K27me3 PcG mark on these ULT1 targets
(Carles and Fletcher, 2009;Pu et al., 2013), evidencing the ability
of ULT1 to regulate these epigenetic marks. Interestingly, the 50-
GAGAG-30Arabidopsis PRE motifs recognized by CLF and its
functional homolog SWINGER (SWN), as well as by other core
components of PcG (Deng et al., 2013;Xiao et al., 2017;Shu et al.,
2019), can also be recognized by the OsULT1 SAND-domain
(Roy et al., 2019). Given that the ULT1 SAND-domains from rice
and Arabidopsis share 90.91% of similarity (Figure 2A), it could
be predicted that Arabidopsis ULT1 can bind through its SAND
domain to the same sites as PcG proteins and thereby interfere
with H3K27me3 marks.
All of these reports indicate that ULT1 is a unique SAND-
domain protein that is part of a TrxG complex; neither in animals
nor in yeast is there evidence of SAND-domain proteins in the
TrxG complexes described so far.
DIFFERENT TISSUES, DIFFERENT ULT1
MECHANISMS
Although ULT1 is able to bind to ATX1, its interactions with
other TrxG components are unclear. Unlike the other members
of the TrxG, ULT1 has a very discrete expression pattern, being
mainly expressed in young organ primordia and shoot and root
meristems (Carles et al., 2005;Ornelas-Ayala et al., 2020). This
suggests that ULT1 has a tissue-specific regulation rather than a
general expression pattern as do the other TrxG members.
Genome-wide analyses have revealed that ULT1-regulated
genes are involved in different developmental processes (Tyler
et al., 2019). Besides its function in SAM development (Fletcher,
2001), ULT1 participates in different stress processes (Pu et al.,
2013;Tyler et al., 2019). In addition, we recently found that
ULT1 is necessary for root stem cell niche (SCN) maintenance
(Figure 3C), including the cell division rate of the Quiescent
Center (QC) and the undifferentiated state of the columella stem
cells (Ornelas-Ayala et al., 2020). Interestingly and in contrast
to its role in the SAM, our genetic analyses of atx1 and ult1
single and double mutants revealed that in the root apical
meristem (RAM) ULT1 acts independently of ATX1 (Ornelas-
Ayala et al., 2020). The ult1 mutants showed a diminished
response to auxins, demonstrated by a down regulation of some
efflux PIN transporter genes and the DR5-GUS reporter, as well
as a premature columella stem cell differentiation (Ornelas-Ayala
et al., 2020). Contrary to this, atx1 mutants do not seem to
have defects in auxin response, whereas the columella stem cell
differentiation seems to be delayed; besides, in contrast to atx1
mutants, ult1 plants did not show any changes in the root and
RAM length (Napsucialy-Mendivil et al., 2014;Ornelas-Ayala
et al., 2020).
Although the studies of the relationship between ULT1 and
ATX1 in the SAM were carried out by single mutant analysis
and biochemical methods, and in the RAM were carried out
by genetic analysis of double mutants, with these studies, it is
possible to establish that ULT1can act by different mechanisms in
the SAM and in the RAM, one of which requires ATX1 to regulate
some aspects of floral development while in the other, ULT1
maintains SCN homeostasis in ATX1-independent manner.
In this regard, 18.7% (2859) of Arabidopsis genes are
deregulated in atx1 loss-of-function mutants, whereas 5.6% (856)
are deregulated in ult1 mutants, and among them only a little
subset is shared (1.1%; 170 genes) in both atx1 and ult1 mutants
(Xu et al., 2018); although this does not mean that it is a direct
regulation by ATX1 or ULT1, it reflects the behavior of genes that
do not always act together. In fact, by ChIP-seq analysis, it has also
been determined that out of the 2,276 Arabidopsis TFs annotated
(Perez-Rodriguez et al., 2010;Jin et al., 2017), ATX1 is bound to
43 (1.88%) of these, whereas ULT1 to 67 (2.9%) and only in 18
(0.8%) of these are bound both ATX1 and ULT1 (Xu et al., 2018),
evidencing that ATX1 and ULT1 have independent targets.
The ATX1-independent function of ULT1 raises the question
whether ULT1 acts together with other HMTs of the TrxG
complex or by a TrxG-independent mechanism or both in
different developmental processes. The analysis of ULT1 protein
interactions in different developmental contexts could provide
evidence compatible with both mechanisms as shown below.
ULT1 ACTS TOGETHER WITH SOME
TRANSCRIPTION FACTORS
The presence of the B-box motif in ULT1 suggests multiple
interactions with other proteins. Indeed, ULT1 interacts
with some TFs (Figure 3B). One of these is the GARP
family transcription factor KANADI1 (KAN1), described as a
transcriptional repressor, involved in the patterning of the abaxial
polarity of leaves and the gynoecium (Eshed et al., 2001;Pires
et al., 2014;Xie et al., 2015). ULT1 interacts physically with KAN1
and genetic analysis indicates that they participate together in the
apical-basal polarity of the gynoecium, restricting the SPATULA
(SPA) expression, which promotes carpel marginal tissue apical
style and stigma tissue formation (Figure 3B). But also, ULT1 and
KAN1 may act antagonistically to regulate the adaxial-abaxial
axis of the gynoecium (Pires et al., 2014;Figure 3B). ULT2 also
physically interacts with KAN1, performing redundant roles on
the apical-basal gynoecium patterning (Monfared et al., 2013;
Pires et al., 2014).
Furthermore, the physical interaction of ULT1 with the
MYB domain-containing TF ULTRAPETALA INTERACTING
FACTOR 1 (UIF1) has been reported. UIF1 binds to WUS and AG
regulatory sequences in the floral meristem (Moreau et al., 2016).
Given that UIF1 acts as a transcriptional repressor, it has been
suggested that it represses WUS expression when interacting with
ULT1, to establish floral meristem determinacy (Moreau et al.,
2016;Figure 3B).
These reports have led to suggestions that ULT1 can act
as a link between chromatin-remodeling factors and some
TFs (Pires et al., 2014). However, other evidence will be needed
to indicate whether the combined function of ULT1 with
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these TFs depends on the other components of TrxG or is
TrxG-independent.
CAN ULT1 ACT IN DIFFERENT TrxG
COMPLEXES?
The lower levels of H3K4me3 marks detected in some genes in
the ult1 mutants compared with those observed in atx1 mutants
(Xu et al., 2018) support the idea that ULT1 can act together
with TrxG complex but independently of ATX1, suggesting the
existence of different TrxG complexes, through which ULT1 can
perform its function. In this regard, multiple SET or MLL HMT
homologues from yeasts and animals that can form different
COMPASS-like complexes and predict the existence of different
TrxG complexes in plants (Schuettengruber et al., 2011). The
Arabidopsis compass-like complex reported so far contains ATX1
as the H3K4me3 HMT (Jiang et al., 2009, 2011); however, there
are other HMTs of H3K4, such as ATX1/SDG27, ATX2/SDG30,
ATXR3/SDG2 and ATXR7/SDG25, that could form different
COMPASS complexes (Sanchez et al., 2015). Indeed, it has been
demonstrated that the SAND domain of OsULT1 is responsible
for interacting with the SET-domain of OsTRX1, an ATX1
ortholog (Roy et al., 2019). The high similarity of Arabidopsis and
rice SAND-domains of ULT1 (Figure 2A) suggests that ULT1 can
also interact with different proteins with a SET-domain.
Of particular interest is ATXR3/SDG2, reported as the main
HMT of the Arabidopsis (Guo et al., 2010). ATXR3/SDG2
does not have a significant sequence homology with other
SDGs outside of the SET domain. However, the gene
encoding this protein is broadly expressed and is crucial
for multiple Arabidopsis developmental processes, regulating
46.4% of all H3K4me3 sites in the Arabidopsis genome
(Berr et al., 2010;Guo et al., 2010;Chen et al., 2017). In
root tissues, the sdg2 loss-of-function mutant shares some
phenotypes with ult1 mutants, such as disorganization of the
SCN, early differentiation of the columella stem cells, and
diminished auxin response (Yao et al., 2013;Ornelas-Ayala
et al., 2020). Although it is still unknown whether ULT1
interacts with SDG2, the similarities in their phenotypes
raises the possibility that ULT1 could act with SDG2 in some
developmental contexts.
DOES ULT1 FUNCTION AS A
MOLECULAR EPIGENETIC SWITCH?
Besides the interactions with TFs and TrxG factors, ULT1 also
interacts with EMF1 (Xu et al., 2018). EMF1 is the plant-
specific protein proposed as a component of Polycomb repressive
complex 1 (PRC1), acting as a bridge to the Polycomb repressive
complex 2 (PRC2) (Calonje et al., 2008;Wang et al., 2014).
Although the relevance of such interaction is unknown, the
H3K27me3 abundancy on some EMF1-target genes associated
with seed development decreases more in the emf1/ult1/atx1
triple mutant than in emf1,atx1, or ult1 single mutant (Xu
et al., 2018). In this framework, it has been proposed that ULT1
interacts with ATX1 to form a complex with PRC2 through
EMF1 to maintain the H3K27me3 marks and a chromatin
repressive state (Xu et al., 2018). This model suggests that
ULT1 not only acts to antagonize the PcG activity; instead, it
could act together with PRC2, maintaining the repression states
of some targets, through the maintenance of the H3K27me3
mark (Figure 3D). For instance, it has been seen that the ult1
mutants have more upregulated genes than down-regulated genes
(Xu et al., 2018;Tyler et al., 2019). Interestingly, the MADS-
box FLOWERING LOCUS C (FLC) gene, which is activated by
TrxG and repressed by PcG (Whittaker and Dean, 2017), is
upregulated (∼4.35 fold) in ult1 mutant plants (Pu et al., 2013;
Xu et al., 2018;Tyler et al., 2019), contrary to what is expected
for TrxG mutants. Besides, ULT1 binding to the FLC locus
supports a direct regulation (Xu et al., 2018). Moreover, the FLC
upregulation is higher in ult1/emf1 double mutants than in the
emf1 single mutant (Pu et al., 2013). Hence, loss of ULT1 function
enhances emf1 upregulation on FLC. In contrast, a different
behavior was observed on genes that are positively regulated
by ULT1, e.g., AG, whose upregulation in emf1 loss-of-function
mutants is abated in the double mutant ult1/emf1 plants (Pu
et al., 2013). Although additional experiments are needed, these
observations support the involvement of ULT1 in transcriptional
repression. Moreover, the repressive function of ULT1 could be
compatible with WUS repression via UIF1 (Moreau et al., 2016),
where PcG could also be participating, as it has been reported
(Xu and Shen, 2008).
Given these observations, we suggest two modes of ULT1
action: one through TrxG to regulate transcriptional activation
via H3K4me3 deposition, which can be ATX1 dependent
or independent, and another, through PcG via EMF1 to
repress transcription.
The apparent dual function of ULT1 has led us to wonder
whether ULT1 can act as a molecular epigenetic switch,
regulating transcriptional repression and activation via PcG
and TrxG, respectively. The presence of molecular epigenetic
switches allows a dynamic regulation, capable of changing gene
expression quickly and efficiently to face different environmental
and developmental states. The existence of bivalent chromatin
domains provides persuasive evidence of molecular epigenetic
switches that regulate gene expression (Hoffmann et al., 2015).
The bivalent domains produced by TrxG and PcG serve to
keep developmental genes on standby, primed for subsequent
expression and to protect against unscheduled expression,
reducing transcriptional noise in favor of robust developmental
decisions (Hoffmann et al., 2015). Although in plant biological
studies, bivalent marks in the same locus have been little
addressed and still remain elusive, finding proteins involved in
both activation and repression processes shows the relevance
of bivalent marks to regulating gene expression quickly and
efficiently. In this regard, ULT1 fulfills the main features to act
as a molecular epigenetic switch: (i) interaction with both TrxG
and PcG proteins, (ii) the ability to increase or decrease gene
expression, and (iii) the ability to regulate the deposition of
H3K4me3 and H3K27me3 marks. However, establishing whether
these characteristics converge into specific genes in time and/or
space is still necessary, in such a way that ULT1 can be a link to
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load the TrxG or PcG complexes and consequently regulate gene
expression accordingly.
CONCLUSION AND PERSPECTIVES
Current knowledge reveals ULT1 to be a versatile protein able
to interact with TFs, TrxG, and PcG proteins to regulate gene
expression of several developmental processes: (1) ULT1 activates
genes related to floral development through its interaction with
ATX1, (2) in association with UIF1, ULT1 represses WUS
expression to regulate shoot and floral meristem homeostasis, (3)
ULT1 is also involved in the regulation of gynoecium patterning,
in which it interacts with KAN1 to repress SPT, (4) ULT1
together with EMF1 maintains repressive marks of some genes
related to seed development, and (5) ULT1, independently of
ATX1, is involved in the root SCN maintenance (Figure 3). The
ability of ULT1 to regulate both gene expression and repression
by modulation of H3K4me3 and H3K27me3 bivalent marks
makes this protein a suitable candidate to regulate bivalent genes
that can be in a poised state, waiting for future instructions
from the cell. The role of ULT1, independent of ATX1 in
roots tissues, suggests a function with other TrxG factors,
evidencing the possible existence of different TrxG complexes
that could be formed in a tissue-specific fashion in which ULT1
could be involved.
The complexity of ULT1 interactions, the phenotypes reported
for ult1 mutants, and their genome-wide effects make it difficult
to define modes of action of ULT1. However, these reports
illustrate four possible ways of action for ULT1: (i) together with
TrxG factors, (ii) with PcG factors, (iii) outside of both TrxG/PcG
complex, and (iv) in association with TFs. Furthermore, a
possible mechanism cannot be ruled out through which ULT1
and TrxG or PcG converge in association with TFs.
It would be important to study specific ULT1 targets
in different developmental and/or tissue-specific stages
to analyze the ULT1 involvement on its activation or
repression, which could shed light on the role of ULT1 in
association with TrxG and PcG complexes, as a molecular
epigenetic switch. Therefore, the future challenge is to define
whether ULT1 acts by different mechanisms or in a single
mechanism that involves all reported interactions. In this
regard, additional research is needed to define whether these
mechanisms can coexist or are tissue-, cell type-, or loci-
specific.
AUTHOR CONTRIBUTIONS
DO-A and MPS conceived and wrote the review. AG-A, ERA-B,
and BG-P wrote the review. All authors have read and approved
this version of the manuscript.
FUNDING
This work was supported by UNAM-DGAPA-PAPIIT IN203220,
IN206220, IN200920, and IN211721. CONACyT 102987 and
102959.
ACKNOWLEDGMENTS
We thank Diana B. Sánchez Rodríguez for her logistical support.
Diego Ornelas-Ayala is a Ph.D. student from the Posgrado
en Ciencias Biomédicas, Universidad Nacional Autónoma de
México, Mexico, and recipient of a fellowship from CONACyT
(588728), Mexico.
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Conflict of Interest: The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be construed as a
potential conflict of interest.
Copyright © 2021 Ornelas-Ayala, Garay-Arroyo, García-Ponce, R Álvarez-Buylla
and Sanchez. This is an open-access article distributed under the terms of the Creative
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