Genomes and Genes
Gene Symbol: Lhx6
Description: LIM homeobox protein 6
Alias: Lhx6.1, LIM/homeobox protein Lhx6, LIM-homeodomain protein 6.1, LIM/homeobox protein Lhx6.1
- Azim E, Jabaudon D, Fame R, Macklis J. SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development. Nat Neurosci. 2009;12:1238-47 pubmed publisher..These data indicate that SOX6 is a central regulator of both progenitor and cortical interneuron diversity during neocortical development. ..
- Yu W, Wang Y, McDonnell K, Stephen D, Bai C. Patterning of ventral telencephalon requires positive function of Gli transcription factors. Dev Biol. 2009;334:264-75 pubmed publisher..Together, these studies unravel a role for Gli transcription factors in mediating Shh signaling to control specification, differentiation and positioning of ventral telencephalic neurons. ..
- Remedios R, Subramanian L, Tole S. LIM genes parcellate the embryonic amygdala and regulate its development. J Neurosci. 2004;24:6986-90 pubmed..The combinatorial expression patterns of LIM genes suggest a comprehensive mechanism for patterning this structure. ..
- Kitamura K, Yanazawa M, Sugiyama N, Miura H, Iizuka Kogo A, Kusaka M, et al. Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. Nat Genet. 2002;32:359-69 pubmed..The present report is, to our knowledge, the first to use phenotypic analysis of a knockout mouse to identify a gene associated with an X-linked human brain malformation...
- Liodis P, Denaxa M, Grigoriou M, Akufo Addo C, Yanagawa Y, Pachnis V. Lhx6 activity is required for the normal migration and specification of cortical interneuron subtypes. J Neurosci. 2007;27:3078-89 pubmed..Here, we show that Lhx6, a gene induced in the medial ganglionic eminence and maintained in parvalbumin- and somatostatin-positive ..
- Chen L, Liao G, Waclaw R, Burns K, Linquist D, Campbell K, et al. Rac1 controls the formation of midline commissures and the competency of tangential migration in ventral telencephalic neurons. J Neurosci. 2007;27:3884-93 pubmed..Moreover, they indicate that Rac1 has a critical role in axon guidance and in acquisition of migratory competency during differentiation of the progenitors for the ventral telencephalon-derived interneurons. ..
- Tucker A, Yamada G, Grigoriou M, Pachnis V, Sharpe P. Fgf-8 determines rostral-caudal polarity in the first branchial arch. Development. 1999;126:51-61 pubmed
- Tiveron M, Rossel M, Moepps B, Zhang Y, Seidenfaden R, Favor J, et al. Molecular interaction between projection neuron precursors and invading interneurons via stromal-derived factor 1 (CXCL12)/CXCR4 signaling in the cortical subventricular zone/intermediate zone. J Neurosci. 2006;26:13273-8 pubmed..These results represent the first evidence for a molecular interaction between precursors of projection neurons and invading interneurons during corticogenesis. ..
- Alifragis P, Liapi A, Parnavelas J. Lhx6 regulates the migration of cortical interneurons from the ventral telencephalon but does not specify their GABA phenotype. J Neurosci. 2004;24:5643-8 pubmed..A member of this family of transcription factors, lhx6, is expressed in the medial ganglionic eminence (MGE) of the ventral telencephalon, where the vast majority of ..
- Nery S, Fishell G, Corbin J. The caudal ganglionic eminence is a source of distinct cortical and subcortical cell populations. Nat Neurosci. 2002;5:1279-87 pubmed..Moreover, we report that the migratory fate of cells from the CGE is intrinsically determined by embryonic day 13.5 (E13.5). Together, these results provide the first insights into the development and fate of the CGE. ..
- Fode C, Ma Q, Casarosa S, Ang S, Anderson D, Guillemot F. A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Genes Dev. 2000;14:67-80 pubmed
- Cobos I, Calcagnotto M, Vilaythong A, Thwin M, Noebels J, Baraban S, et al. Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. Nat Neurosci. 2005;8:1059-68 pubmed..Dlx1 mutant mice show generalized electrographic seizures and histological evidence of seizure-induced reorganization, linking the Dlx1 mutation to delayed-onset epilepsy associated with interneuron loss. ..
- Xu Q, Wonders C, Anderson S. Sonic hedgehog maintains the identity of cortical interneuron progenitors in the ventral telencephalon. Development. 2005;132:4987-98 pubmed..These results combine in vitro and ex vivo analyses to link embryonic abnormalities in Shh signaling to postnatal alterations in cortical interneuron composition. ..
- Sussel L, Marin O, Kimura S, Rubenstein J. Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum. Development. 1999;126:3359-70 pubmed..We present evidence that these phenotypes result from a ventral-to-dorsal transformation of the pallidal primordium into a striatal-like anlage. ..
- Nery S, Corbin J, Fishell G. Dlx2 progenitor migration in wild type and Nkx2.1 mutant telencephalon. Cereb Cortex. 2003;13:895-903 pubmed..This recovery may be, at least in part, a result of the late migration of Dlx2 progenitors from the caudal ganglionic eminences (CGE), which, based on our previous work, does not appear to require Nkx2.1 gene function. ..
- Trumpp A, Depew M, Rubenstein J, Bishop J, Martin G. Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch. Genes Dev. 1999;13:3136-48 pubmed..Because the mutant mice resemble humans with first arch syndromes that include agnathia, our results raise the possibility that some of these syndromes are caused by mutations that affect FGF8 signaling in BA1 ectoderm...
- Denaxa M, Kalaitzidou M, Garefalaki A, Achimastou A, Lasrado R, Maes T, et al. Maturation-promoting activity of SATB1 in MGE-derived cortical interneurons. Cell Rep. 2012;2:1351-62 pubmed publisher..The LIM-homeodomain protein LHX6 is critical for the development of all cortical interneurons originating in the medial ganglionic eminence, but the ..
- Flames N, Long J, Garratt A, Fischer T, Gassmann M, Birchmeier C, et al. Short- and long-range attraction of cortical GABAergic interneurons by neuregulin-1. Neuron. 2004;44:251-61 pubmed..These observations provide evidence that Neuregulin-1 and its ErbB4 receptor directly control neuronal migration in the nervous system. ..
- Cobos I, Long J, Thwin M, Rubenstein J. Cellular patterns of transcription factor expression in developing cortical interneurons. Cereb Cortex. 2006;16 Suppl 1:i82-8 pubmed..and mature neocortical interneurons of 8 transcription factors, including 6 homeobox (Dlx1, Dlx2, Dlx5, Arx, Lhx6, Cux2), 1 basic helix-loop-helix, (NPAS1), and 1 bZIP (MafB)...
- Zhao Y, Flandin P, Long J, Cuesta M, Westphal H, Rubenstein J. Distinct molecular pathways for development of telencephalic interneuron subtypes revealed through analysis of Lhx6 mutants. J Comp Neurol. 2008;510:79-99 pubmed publisherHere we analyze the role of the Lhx6 lim-homeobox transcription factor in regulating the development of subsets of neocortical, hippocampal, and striatal interneurons...
- Cobos I, Borello U, Rubenstein J. Dlx transcription factors promote migration through repression of axon and dendrite growth. Neuron. 2007;54:873-88 pubmed
- Du T, Xu Q, Ocbina P, Anderson S. NKX2.1 specifies cortical interneuron fate by activating Lhx6. Development. 2008;135:1559-67 pubmed publisher..The LIM-homeobox gene Lhx6 is induced by this rescue experiment, and gain- and loss-of-function studies suggest that Lhx6 is necessary and ..
- Flames N, Pla R, Gelman D, Rubenstein J, Puelles L, Marin O. Delineation of multiple subpallial progenitor domains by the combinatorial expression of transcriptional codes. J Neurosci. 2007;27:9682-95 pubmed..Furthermore, the results of microtransplantation experiments in vivo corroborate that anatomically defined regions of the mouse subpallium, such as the medial ganglionic eminence, can be subdivided into functionally distinct domains. ..
- Remedios R, Huilgol D, Saha B, Hari P, Bhatnagar L, Kowalczyk T, et al. A stream of cells migrating from the caudal telencephalon reveals a link between the amygdala and neocortex. Nat Neurosci. 2007;10:1141-50 pubmed..This is first evidence of a dorsal pallial contribution to the amygdala, demonstrating a developmental and mechanistic link between the amygdala and the neocortex. ..
- Batista Brito R, Rossignol E, Hjerling Leffler J, Denaxa M, Wegner M, Lefebvre V, et al. The cell-intrinsic requirement of Sox6 for cortical interneuron development. Neuron. 2009;63:466-81 pubmed publisher..Both its expression pattern and null phenotype suggests that Sox6 gene function is closely linked to that of Lhx6. In both Lhx6 and Sox6 null animals, the expression of PV and SST and the position of both basket and Martinotti ..
- García López M, Abellan A, Legaz I, Rubenstein J, Puelles L, Medina L. Histogenetic compartments of the mouse centromedial and extended amygdala based on gene expression patterns during development. J Comp Neurol. 2008;506:46-74 pubmed..1, Lhx6, Lhx7/8, Lhx9, Shh, and Gbx1), as well as genes considered markers for specific subpallial neuronal subpopulations...
- Vidaki M, Tivodar S, Doulgeraki K, Tybulewicz V, Kessaris N, Pachnis V, et al. Rac1-dependent cell cycle exit of MGE precursors and GABAergic interneuron migration to the cortex. Cereb Cortex. 2012;22:680-92 pubmed publisher..Rac1 is necessary for their transition from G1 to S phase, at least in part by regulating cyclin D levels and retinoblastoma protein phosphorylation. ..
- Grigoriou M, Tucker A, Sharpe P, Pachnis V. Expression and regulation of Lhx6 and Lhx7, a novel subfamily of LIM homeodomain encoding genes, suggests a role in mammalian head development. Development. 1998;125:2063-74 pubmed..We have identified two genes belonging to a novel subfamily of mammalian Lhx genes, designated Lhx6 and Lhx7...
- Wang Y, Li G, Stanco A, Long J, Crawford D, Potter G, et al. CXCR4 and CXCR7 have distinct functions in regulating interneuron migration. Neuron. 2011;69:61-76 pubmed publisher..On the other hand, CXCL12 stimulation of CXCR7, but not CXCR4, promoted MAP kinase signaling. Thus, we suggest that CXCR4 and CXCR7 have distinct roles and signal transduction in regulating interneuron movement and laminar positioning. ..
- Choi G, Dong H, Murphy A, Valenzuela D, Yancopoulos G, Swanson L, et al. Lhx6 delineates a pathway mediating innate reproductive behaviors from the amygdala to the hypothalamus. Neuron. 2005;46:647-60 pubmed..Using genetically encoded and conventional axonal tracers, we have found that the transcription factor Lhx6 delineates the reproductive branch of this pathway...
- Arguello A, Yang X, Vogt D, Stanco A, Rubenstein J, Cheyette B. Dapper antagonist of catenin-1 cooperates with Dishevelled-1 during postsynaptic development in mouse forebrain GABAergic interneurons. PLoS ONE. 2013;8:e67679 pubmed publisher..In sum, our results support a novel cell-autonomous postsynaptic role for Dact1, in cooperation with Dishevelled-1 and possibly Disrupted in Schizophrenia-1, in the formation of synapses on cortical interneuron dendrites. ..
- Kanatani S, Honda T, Aramaki M, Hayashi K, Kubo K, Ishida M, et al. The COUP-TFII/Neuropilin-2 is a molecular switch steering diencephalon-derived GABAergic neurons in the developing mouse brain. Proc Natl Acad Sci U S A. 2015;112:E4985-94 pubmed publisher..Taken together, these results reveal that COUP-TFII/Nrp2 is a molecular switch determining the pathway and destination of migrating GABAergic neurons born in the POa. ..
- Cesario J, Almaidhan A, Jeong J. Expression of forkhead box transcription factor genes Foxp1 and Foxp2 during jaw development. Gene Expr Patterns. 2016;20:111-9 pubmed publisher..Together, we demonstrated for the first time that Foxp1 and Foxp2 are expressed during craniofacial development. Our data suggest that the Foxp genes may regulate development of the aboral and posterior regions of the jaw. ..
- Colombo E, Collombat P, Colasante G, Bianchi M, Long J, Mansouri A, et al. Inactivation of Arx, the murine ortholog of the X-linked lissencephaly with ambiguous genitalia gene, leads to severe disorganization of the ventral telencephalon with impaired neuronal migration and differentiation. J Neurosci. 2007;27:4786-98 pubmed..Altogether, these results highlight the critical functions of Arx in promoting neural migration and regulating basal ganglia differentiation in mice, consistent with the phenotype of XLAG patients...
- Bielle F, Marcos Mondejar P, Keita M, Mailhes C, Verney C, Nguyen Ba Charvet K, et al. Slit2 activity in the migration of guidepost neurons shapes thalamic projections during development and evolution. Neuron. 2011;69:1085-98 pubmed publisher..Our study reveals that subtle differences in the migration of conserved intermediate target neurons trigger large-scale changes in thalamic connectivity, and opens perspectives on Slit functions and the evolution of brain wiring. ..
- Tuncdemir S, Fishell G, Batista Brito R. miRNAs are Essential for the Survival and Maturation of Cortical Interneurons. Cereb Cortex. 2015;25:1842-57 pubmed publisher..Thus, our results indicate that cIN progenitors require Dicer-dependent mechanisms to fine-tune the migration and maturation of cINs. ..
- Silberberg S, Taher L, Lindtner S, Sandberg M, Nord A, Vogt D, et al. Subpallial Enhancer Transgenic Lines: a Data and Tool Resource to Study Transcriptional Regulation of GABAergic Cell Fate. Neuron. 2016;92:59-74 pubmed publisher..factors that regulate subpallial patterning and differentiation and analysis of enhancer activity in Dlx1/2 and Lhx6 mutants, we elucidated novel molecular mechanisms that regulate region-specific enhancer activity in the developing ..
- Aggarwal V, Carpenter C, Freyer L, Liao J, Petti M, Morrow B. Mesodermal Tbx1 is required for patterning the proximal mandible in mice. Dev Biol. 2010;344:669-81 pubmed publisher..5. This occurs without significant changes in cell proliferation or apoptosis at the same stage. Our results elucidate a new function for the non-neural crest core mesoderm and specifically, mesodermal Tbx1, in shaping the lower jaw. ..
- Mori T, Yuxing Z, Takaki H, Takeuchi M, Iseki K, Hagino S, et al. The LIM homeobox gene, L3/Lhx8, is necessary for proper development of basal forebrain cholinergic neurons. Eur J Neurosci. 2004;19:3129-41 pubmed..Neurotransmitter phenotypes other than cholinergic in the basal forebrain appeared intact. From these results, we suggested that L3/Lhx8 has a pivotal and specific role in the development and/or maintenance of BFCNs. ..
- Vogt D, Hunt R, Mandal S, Sandberg M, Silberberg S, Nagasawa T, et al. Lhx6 directly regulates Arx and CXCR7 to determine cortical interneuron fate and laminar position. Neuron. 2014;82:350-64 pubmed publisher..b>Lhx6, a LIM-homeodomain transcription factor, is essential for specification of MGE-derived somatostatin and parvalbumin ..
- Zhou C, Yang G, Chen M, He L, Xiang L, Ricupero C, et al. Lhx6 and Lhx8: cell fate regulators and beyond. FASEB J. 2015;29:4083-91 pubmed publisher..b>Lhx6 and -8 play overlapping and distinctive roles, but in general act as cell fate mediators and in turn are regulated ..
- Gopal P, Golden J. Pax6-/- mice have a cell nonautonomous defect in nonradial interneuron migration. Cereb Cortex. 2008;18:752-62 pubmed..Further, our data indicate that the known axonal disorganization in Sey-/- mice contributes to the observed reduced distance of NRCM. ..
- Petryniak M, Potter G, Rowitch D, Rubenstein J. Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain. Neuron. 2007;55:417-33 pubmed..Our results identify another role for Dlx genes as modulators of neuron versus oligodendrocyte development in the ventral embryonic forebrain. ..
- van den Berghe V, Stappers E, Vandesande B, Dimidschstein J, Kroes R, Francis A, et al. Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1. Neuron. 2013;77:70-82 pubmed publisher..Our results reveal that Sip1, through tuning of Unc5b levels, is essential for cortical interneuron guidance. ..
- Gong S, Zheng C, Doughty M, Losos K, Didkovsky N, Schambra U, et al. A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature. 2003;425:917-25 pubmed..The atlas, library of BAC vectors and BAC transgenic mice generated in this screen provide a rich resource that allows a broad array of investigations not previously available to the neuroscience community. ..
- Denaxa M, Kyriakopoulou K, Theodorakis K, Trichas G, Vidaki M, Takeda Y, et al. The adhesion molecule TAG-1 is required for proper migration of the superficial migratory stream in the medulla but not of cortical interneurons. Dev Biol. 2005;288:87-99 pubmed..Therefore, TAG-1 function is required for the survival of the neurons of some precerebellar nuclei, while it is not required for cortical interneuron migration in vivo. ..
- Oishi K, Watatani K, Itoh Y, Okano H, Guillemot F, Nakajima K, et al. Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash1. Proc Natl Acad Sci U S A. 2009;106:13064-9 pubmed publisher..These results have unveiled an unexpected role of the PDK1-Akt pathway: a key mediator of extracellular signals regulating the production of neocortical GABAergic neurons. ..
- Zhao T, Kraemer N, Oldekamp J, Cankaya M, Szabo N, Conrad S, et al. Emx2 in the developing hippocampal fissure region. Eur J Neurosci. 2006;23:2895-907 pubmed..Additionally, we show differential mutant phenotypes of both Emx2 and Pax6 in neocortical vs. hippocampal Reln-expressing cells, indicating differential development of both subpopulations. ..
- Kimura N, Ueno M, Nakashima K, Taga T. A brain region-specific gene product Lhx6.1 interacts with Ldb1 through tandem LIM-domains. J Biochem. 1999;126:180-7 pubmed..We have now identified a novel LHX molecule, termed Lhx6.1, that is closely related to a recently reported Lhx6 molecule. The Lhx6...
- Henry A, Hohmann J. High-resolution gene expression atlases for adult and developing mouse brain and spinal cord. Mamm Genome. 2012;23:539-49 pubmed publisher..All data and tools are freely available via the Allen Brain Atlas portal (www.brain-map.org). ..
- Lopes R, Verhey van Wijk N, Neves G, Pachnis V. Transcription factor LIM homeobox 7 (Lhx7) maintains subtype identity of cholinergic interneurons in the mammalian striatum. Proc Natl Acad Sci U S A. 2012;109:3119-24 pubmed publisher..of several subtype-specific markers, including choline acetyl transferase and Isl1, and are respecified into Lhx6-expressing mature GABAergic interneurons...
- Bithell A, Alberta J, Hornby F, Stiles C, Williams B. Expression of the guanine nucleotide exchange factor, mr-gef, is regulated during the differentiation of specific subsets of telencephalic neurons. Brain Res Dev Brain Res. 2003;146:107-18 pubmed..of mr-gef during early telencephalic neurogenesis is strikingly similar to that of GABA and the LIM homeobox gene Lhx6, a transcription factor expressed by GABAergic interneurons generated in the ventral telencephalon, some of which ..
- Liu K, Kim J, Kim D, Zhang Y, Bao H, Denaxa M, et al. Lhx6-positive GABA-releasing neurons of the zona incerta promote sleep. Nature. 2017;548:582-587 pubmed publisher..show that a subset of GABAergic neurons in the mouse ventral zona incerta, which express the LIM homeodomain factor Lhx6 and are activated by sleep pressure, both directly inhibit wake-active hypocretin and GABAergic cells in the ..
- Kawase Koga Y, Otaegi G, Sun T. Different timings of Dicer deletion affect neurogenesis and gliogenesis in the developing mouse central nervous system. Dev Dyn. 2009;238:2800-12 pubmed publisher..Our studies of different timings of Dicer deletion demonstrate the importance of the Dicer-mediated microRNA pathway in regulating distinct phases of neurogenesis and gliogenesis during the CNS development. ..
- Fuccillo M, Rutlin M, Fishell G. Removal of Pax6 partially rescues the loss of ventral structures in Shh null mice. Cereb Cortex. 2006;16 Suppl 1:i96-102 pubmed..Together, our findings are consistent with Pax6 function being required for aspects of Gli3-mediated telencephalic patterning. ..
- Abe P, Mueller W, Schütz D, Mackay F, Thelen M, Zhang P, et al. CXCR7 prevents excessive CXCL12-mediated downregulation of CXCR4 in migrating cortical interneurons. Development. 2014;141:1857-63 pubmed publisher..Our findings imply that interfering with the CXCL12-scavenging activity of CXCR7 causes loss of CXCR4 function as a consequence of excessive CXCL12-mediated CXCR4 activation and degradation. ..
- Lopez Bendito G, Cautinat A, Sanchez J, Bielle F, Flames N, Garratt A, et al. Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation. Cell. 2006;125:127-42 pubmed..These results show that neuronal tangential migration constitutes a novel mechanism to control the timely arrangement of guidance cues required for axonal tract formation in the mammalian brain. ..
- Takagi T, Nishizaki Y, Matsui F, Wakamatsu N, Higashi Y. De novo inbred heterozygous Zeb2/Sip1 mutant mice uniquely generated by germ-line conditional knockout exhibit craniofacial, callosal and behavioral defects associated with Mowat-Wilson syndrome. Hum Mol Genet. 2015;24:6390-402 pubmed publisher..To our knowledge, this is the first time an inducible de novo mutation system has been applied to murine germline cells to produce an animal model of a human congenital disease. ..
- Ko S, Chung I, Xu X, Oka S, Zhao H, Cho E, et al. Smad4 is required to regulate the fate of cranial neural crest cells. Dev Biol. 2007;312:435-47 pubmed..Taken together, our data show that TGF-beta/BMP signals rely on Smad-dependent pathways in the ectomesenchyme to mediate epithelial-mesenchymal interactions that control craniofacial organogenesis...
- Katayama K, Imai F, Campbell K, Lang R, Zheng Y, Yoshida Y. RhoA and Cdc42 are required in pre-migratory progenitors of the medial ganglionic eminence ventricular zone for proper cortical interneuron migration. Development. 2013;140:3139-45 pubmed publisher..These findings provide genetic evidence that RhoA and Cdc42 are required in progenitors of the MGE in the VZ, but not the SVZ, for proper cortical interneuron migration. ..
- Seah C, Levy M, Jiang Y, Mokhtarzada S, Higgs D, Gibbons R, et al. Neuronal death resulting from targeted disruption of the Snf2 protein ATRX is mediated by p53. J Neurosci. 2008;28:12570-80 pubmed publisher..Together, these findings show that ATRX deficiency leads to p53-dependent neuronal apoptosis which is responsible for some but not all of the phenotypic consequences of ATRX deficiency in the forebrain. ..
- Zhao H, Oka K, Bringas P, Kaartinen V, Chai Y. TGF-beta type I receptor Alk5 regulates tooth initiation and mandible patterning in a type II receptor-independent manner. Dev Biol. 2008;320:19-29 pubmed publisher..in early mandible patterning and altered expression of key patterning genes including Msx1, Bmp4, Bmp2, Pax9, Alx4, Lhx6/7 and Gsc...
- Coré N, Caubit X, Metchat A, Boned A, Djabali M, Fasano L. Tshz1 is required for axial skeleton, soft palate and middle ear development in mice. Dev Biol. 2007;308:407-20 pubmed..Finally, we demonstrate that Tshz1 is required for the development of the soft palate...
- Narboux Nême N, Goïame R, Mattei M, Cohen Tannoudji M, Wassef M. Integration of H-2Z1, a somatosensory cortex-expressed transgene, interferes with the expression of the Satb1 and Tbc1d5 flanking genes and affects the differentiation of a subset of cortical interneurons. J Neurosci. 2012;32:7287-300 pubmed publisher..Together, our data suggest that regulation of H-2Z1 expression results from local and remote genetic interactions. ..